|
1
|
Faraco G. Dietary salt, vascular dysfunction, and cognitive impairment. Cardiovasc Res 2025; 120:2349-2359. [PMID: 39429024 PMCID: PMC11976728 DOI: 10.1093/cvr/cvae229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/24/2024] [Accepted: 09/15/2024] [Indexed: 10/22/2024] Open
Abstract
Excessive salt consumption is a major health problem worldwide leading to serious cardiovascular events including hypertension, heart disease, and stroke. Additionally, high-salt diet has been increasingly associated with cognitive impairment in animal models and late-life dementia in humans. High-salt consumption is harmful for the cerebral vasculature, disrupts blood supply to the brain, and could contribute to Alzheimer's disease pathology. Although animal models have advanced our understanding of the cellular and molecular mechanisms, additional studies are needed to further elucidate the effects of salt on brain function. Furthermore, the association between excessive salt intake and cognitive impairment will have to be more thoroughly investigated in humans. Since the harmful effects of salt on the brain are independent by its effect on blood pressure, in this review, I will specifically discuss the evidence, available in experimental models and humans, on the effects of salt on vascular and cognitive function in the absence of changes in blood pressure. Given the strong effects of salt on the function of immune cells, I will also discuss the evidence linking salt consumption to gut immunity dysregulation with particular attention to the ability of salt to disrupt T helper 17 (Th17) cell homeostasis. Lastly, I will briefly discuss the data implicating IL-17A, the major cytokine produced by Th17 cells, in vascular dysfunction and cognitive impairment.
Collapse
Affiliation(s)
- Giuseppe Faraco
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA
| |
Collapse
|
|
2
|
Wu J, Wang L, Han X, Huang L, Meng Q, Yang T, Deji Q, Wang Z, Guo B, Zhao X. Hypothetical Behavioral Interventions for Mitigating the Cardiovascular Effects of Long-Term Fine Particulate Matter Exposure: Analyses From 2 Prospective Cohorts. J Am Heart Assoc 2025; 14:e038624. [PMID: 40079333 DOI: 10.1161/jaha.124.038624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 01/30/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND Whether healthy behaviors can attenuate the adverse association between ambient fine particulate matter (PM2.5) and cardiovascular disease (CVD) is inconclusive. METHODS AND RESULTS The parametric g-formula was used to quantify the potential reduction in PM2.5 effect on CVD under different scenarios of hypothetical behavioral interventions (including dietary patterns, physical activity, body mass index, alcohol consumption, smoking, and dietary supplements). Feasible intervention scenarios, defined on the basis of values considered feasible in previous real-world interventions (eg, overweight participants lose 6.69% of their weight). Intensive scenarios, in which all participants are adopting completely healthy behaviors (eg, maintain normal weight). We also estimate the effect of joint interventions that incorporate the above behaviors. Long-term PM2.5 exposure was associated with incident CVD in both cohorts, with the risk difference per 1000 person-years for a 5 μg/m3 increase in PM2.5 being 1.42 (95% CI, 1.04-1.79) in the UKB (UK Biobank) and 2.15 (95% CI, 1.65-2.59) in the Sichuan Cohort (China Multi-Ethnic Cohort, Sichuan Region). In both feasible and intensive scenarios, improving diet, physical activity, and body mass index could significantly reduce the risk difference of PM2.5 on CVD, with the reduced proportion ranging from 4.59% to 37.22%. A feasible joint hypothetical intervention on 6 behaviors would reduce the effect of PM2.5 on CVD by 31.47% (10.13%-57.26%) and 19.75% (10.78%-42.89%) in the low-pollution UK Biobank and high-pollution Sichuan cohort, respectively. A combination of more intensive interventions would reduce risk difference by 57.51% (21.64%-100.69%) and 45.54% (22.66%-106.66%), respectively. CONCLUSIONS Healthier behaviors could serve as individual-level complementary strategies to emission control for minimizing the health impact of PM2.5, whether in high- or low-pollution areas.
Collapse
Affiliation(s)
- Jialong Wu
- West China School of Public Health and West China Fourth Hospital Sichuan University Chengdu Sichuan China
| | - Liang Wang
- Chengdu Center for Disease Control &Prevention Chengdu Sichuan China
| | - Xu Han
- Health Information Center of Sichuan Province Chengdu Sichuan China
| | - Linya Huang
- Health Information Center of Sichuan Province Chengdu Sichuan China
| | - Qiong Meng
- Department of Epidemiology and Health Statistics, School of Public Health Kunming Medical University Kunming Yunnan China
| | - Tingting Yang
- School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education Guizhou Medical University Guiyang China
| | | | - Zihao Wang
- Chongqing Municipal Center for Disease Control and Prevention Chongqing China
| | - Bing Guo
- West China School of Public Health and West China Fourth Hospital Sichuan University Chengdu Sichuan China
| | - Xing Zhao
- West China School of Public Health and West China Fourth Hospital Sichuan University Chengdu Sichuan China
| |
Collapse
|
|
3
|
Butler HM, McCrorey MK, Palygina L, Lacey R, Van Beusecum JP. Salt-sensitive hypertension: role of endothelial and vascular dysfunction and sex. Front Pharmacol 2025; 16:1565962. [PMID: 40144661 PMCID: PMC11936959 DOI: 10.3389/fphar.2025.1565962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
For the last 120 years, the contribution of salt has been identified in the pathophysiological elevation of blood pressure. Since then, both human and experimental murine studies have begun to elucidate the key mechanisms contributing to the development of salt-sensitive hypertension. Numerous mechanisms, including increased plasma volume, sodium retention, impaired autoregulatory capability, inflammation, and endothelial and vascular dysfunction, contribute to deleterious elevations in blood pressure during salt sensitivity. The endothelium plays a critical role in blood flow regulation, renal blood flow, and blood pressure elevations and in migrating immune cells to end-organs, contributing to end-organ damage and fibrosis. In this review, we will consider the clinical studies setting the foundation for the definition of salt-sensitive hypertension, murine models to study endothelial and vascular contributions, and endothelial cell cultures that have shed light on signaling mechanisms. Lastly, we will discuss the sex-dependent physiology and mechanisms contributing to salt-sensitive hypertension development and their clinical implications.
Collapse
Affiliation(s)
- Helen M. Butler
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Marice K. McCrorey
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
- College of Graduate Studies, Medical University of South Carolina, Charleston, SC, United States
| | - Lada Palygina
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Ryan Lacey
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Justin P. Van Beusecum
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
- Ralph H. Johnson VA Healthcare System, Charleston, SC, United States
| |
Collapse
|
|
4
|
McMillan RK, Stock JM, Romberger NT, Wenner MM, Chai SC, Farquhar WB. The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults. Physiol Rep 2025; 13:e70284. [PMID: 40129273 PMCID: PMC11933718 DOI: 10.14814/phy2.70284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 02/25/2025] [Accepted: 03/11/2025] [Indexed: 03/26/2025] Open
Abstract
Increased dietary sodium is linked to hypertension, but most young adults display "sodium-resistant" blood pressure (BP), meaning BP is not elevated with sodium loading. In sodium-resistant rodents, fructose induces salt-sensitive BP via increased renal sodium reabsorption. Therefore, we tested the impact of fructose and sodium on renal sodium handling and BP in healthy adults, hypothesizing that their combination would impair sodium excretion and increase BP. Thirty-six participants enrolled in a randomized, double-blind, crossover trial involving three diets varying in fructose and sodium. On day 7, participants wore ambulatory BP monitors and collected 24-h urine. Although high sodium increased urinary sodium excretion, excretion was 15% lower with high fructose plus high salt versus high salt alone (235.1 ± 85.0 vs. 277.9 ± 121.2 mmol/24 h, p = 0.05). Compared to the recommended diet, high salt alone did not significantly change 24 h. MAP; however, high fructose plus high salt modestly raised 24 h MAP (81 ± 6 vs. 84 ± 7 mmHg, p = 0.03). High fructose and high salt increased serum interleukin-6 concentrations compared to the recommended diet (0.31 ± 0.2 vs. 0.24 ± 0.19 pg/mL, p = 0.04). These findings suggest that increased sodium and fructose alter renal sodium handling and BP in young adults.
Collapse
Affiliation(s)
- Ronald K. McMillan
- Department of Medicine, Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleTennesseeUSA
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Joseph M. Stock
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
- Department of KinesiologyEast Carolina UniversityGreenvilleNorth CarolinaUSA
| | - Nathan T. Romberger
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Megan M. Wenner
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Sheau C. Chai
- Department of Health Behavior and Nutrition SciencesUniversity of DelawareNewarkDelawareUSA
| | - William B. Farquhar
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| |
Collapse
|
|
5
|
Sahu S, Dash K, Mishra M. Common salt (NaCl) causes developmental, behavioral, and physiological defects in Drosophila melanogaster. Nutr Neurosci 2025:1-19. [PMID: 39760749 DOI: 10.1080/1028415x.2024.2441677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
PURPOSE The incidence of obesity has surged to pandemic levels in recent decades. Approximately 1.89 million obesity are linked to excessive salt consumption. This study aims to check the toxicity of salt at different concentrations using an invertebrate model organism Drosophila melanogaster. METHODS Drosophila food was mixed with different salt concentrations (50, 200, 400, 800 µM). The toxicity of salt in third instar larvae was checked via different experiments such as trypan blue assay, crawling assay, and other histological staining was done to check the deposition of lipid droplets and amount of reactive oxygen species. Food intake analysis was performed to check the feeding rate, and body weight was also calculated to check the obesity index. Several behavioral assays are also performed in adult flies. RESULTS Most significant abnormalities were seen at 50 and 200 µM concentrations. Feeding rate increased up to 60%, body weight was increased up to 12% in larvae, and 27% in adult at 200 µM concentration. Approximately 60% larvae and 58% adult flies had defective response to extreme heat. 28% larvae and 38% adult flies were not responding to cold temperature. 55% flies had a defective phototaxis behavior and 40% of them showed positive geotaxis at those range. Salt stress leads to the buildup of free radicals, resulting in DNA damage in both the gut and hemolymph. FINDINGS Most toxic consequences are observed at the lower concentration range as the feeding rate was higher. Flies show aversive response to feed on the higher concentration of salt.
Collapse
Affiliation(s)
- Swetapadma Sahu
- Neural Developmental Biology Lab, Department of Life Science, NIT Rourkela, Rourkela, Odisha, India
| | - Kalpanarani Dash
- Neural Developmental Biology Lab, Department of Life Science, NIT Rourkela, Rourkela, Odisha, India
| | - Monalisa Mishra
- Neural Developmental Biology Lab, Department of Life Science, NIT Rourkela, Rourkela, Odisha, India
| |
Collapse
|
|
6
|
Dunaway LS, Cook AK, Kellum CE, Edell C, Botta D, Molina PA, Sedaka RS, d’Uscio LV, Katusic ZS, Pollock DM, Inscho EW, Pollock JS. Endothelial histone deacetylase 1 activity impairs kidney microvascular NO signaling in rats fed a high-salt diet. Acta Physiol (Oxf) 2024; 240:e14201. [PMID: 39007513 PMCID: PMC11329346 DOI: 10.1111/apha.14201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/12/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024]
Abstract
AIM We aimed to test the hypothesis that a high-salt diet (HS) impairs NO signaling in kidney microvascular endothelial cells through a histone deacetylase 1 (HDAC1)-dependent mechanism. METHODS Male Sprague Dawley rats were fed normal salt diet (NS; 0.49% NaCl) or HS (4% NaCl) for 2 weeks. NO signaling was assessed by measuring L-NAME induced vasoconstriction of the afferent arteriole using the blood perfused juxtamedullary nephron (JMN) preparation. In this preparation, kidneys were perfused with blood from a donor rat on a matching or different diet to that of the kidney donor. Kidney endothelial cells were isolated with magnetic activated cell sorting and HDAC1 activity was measured. RESULTS We found HS-induced impaired NO signaling in the afferent arteriole. This was restored by inhibition of HDAC1 with MS-275. Consistent with these findings, HDAC1 activity was increased in kidney endothelial cells. We further found the loss of NO to be dependent upon the diet of the blood donor rather than the diet of the kidney donor and the plasma from HS-fed rats to be sufficient to induce impaired NO signaling. This indicates the presence of a humoral factor we termed plasma-derived endothelial dysfunction mediator (PDEM). Pretreatment with the antioxidants, PEG-SOD and PEG-catalase, as well as the NOS cofactor, tetrahydrobiopterin, restored NO signaling. CONCLUSION We conclude that HS activates endothelial HDAC1 through PDEM leading to decreased NO signaling. This study provides novel insights into the molecular mechanisms by which a HS decreases renal microvascular endothelial NO signaling.
Collapse
Affiliation(s)
- Luke S. Dunaway
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Anthony K. Cook
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Cailin E. Kellum
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Claudia Edell
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Davide Botta
- Department of Microbiology, Immunology Institute, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Patrick A. Molina
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Randee S. Sedaka
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Livius V. d’Uscio
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN USA
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN USA
| | - Zvonimir S. Katusic
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN USA
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN USA
| | - David M. Pollock
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Edward W. Inscho
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| | - Jennifer S. Pollock
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL USA
| |
Collapse
|
|
7
|
Grano de Oro A, Kumariya S, Mell B, Zubcevic J, Joe B, Osman I. Spontaneous vascular dysfunction in Dahl salt-sensitive male rats raised without a high-salt diet. Physiol Rep 2024; 12:e16165. [PMID: 39048525 PMCID: PMC11268988 DOI: 10.14814/phy2.16165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/09/2024] [Accepted: 07/17/2024] [Indexed: 07/27/2024] Open
Abstract
Dahl salt-sensitive (SS) rats fed a high-salt diet, but not low-salt, exhibit vascular dysfunction. Several substrains of SS rats exist that differ in their blood pressure phenotypes and salt sensitivity. The goal of this study was to investigate whether the John-Rapp-derived SS rat (SS/Jr), which exhibits spontaneous hypertension on a low-salt diet, presents with hallmarks of vascular dysfunction observed in another experimental model of hypertension independent of dietary salt, the spontaneously hypertensive rat (SHR). Endothelium-intact aortic rings and mesenteric resistance arteries were isolated from low-salt fed adult male SS/Jr rats and SHRs, or their respective controls, for isometric wire myography. Vessels were challenged with cumulative concentrations of various vasoactive substances, in the absence or presence of nitric oxide synthase or cyclooxygenase inhibitors. Despite showing some differences in their responses to various vasoactive substances, both SS/Jr rats and SHRs exhibited key features of vascular dysfunction, including endothelial dysfunction and hyperresponsiveness to vasocontractile agonists. In conclusion, this study provides evidence to support the utility of the SS/Jr rat strain maintained on a low-salt diet as a valid experimental model for vascular dysfunction, a key feature of human hypertension.
Collapse
Affiliation(s)
- Arturo Grano de Oro
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| | - Sanjana Kumariya
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| | - Blair Mell
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| | - Jasenka Zubcevic
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| | - Bina Joe
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| | - Islam Osman
- Department of Physiology and Pharmacology, Center for Hypertension and Personalized MedicineUniversity of Toledo, College of Medicine and Life SciencesToledoOhioUSA
| |
Collapse
|
|
8
|
Vulin M, Muller A, Drenjančević I, Šušnjara P, Mihaljević Z, Stupin A. High dietary salt intake attenuates nitric oxide mediated endothelium-dependent vasodilation and increases oxidative stress in pregnancy. J Hypertens 2024; 42:672-684. [PMID: 38230612 DOI: 10.1097/hjh.0000000000003645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
OBJECTIVE This study aimed to investigate the impact of dietary salt intake during normal pregnancy on maternal microvascular and macrovascular endothelium-dependent reactivity and oxidative stress level. MATERIALS AND METHODS In this cross-sectional study, based on their 24-h urinary sodium excretion, pregnant women (37-40 weeks of gestation) were divided into three groups: normal salt (<5.75 g/day, N = 12), high salt (5.75-10.25 g/day, N = 36), and very high salt (VHS;>10.25 g/day, N = 17). Forearm skin microvascular reactivity in response to vascular occlusion, local heating (LTH) and iontophoresis of acetylcholine (AChID), as well as brachial artery flow mediated dilation (FMD) were measured. Serum nitric oxide, endocan, 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid reactive substances (TBARS), and ferric-reducing ability of plasma assay were measured as biomarkers of endothelial function/activation and oxidative stress. RESULTS Brachial artery FMD, microvascular AChID, and LTH were significantly decreased in VHS compared with NS group, while LTH was also decreased in normal salt compared with high salt group. Nitric oxide was significantly decreased in both high salt and VHS groups compared with normal salt. Endocan, 8-iso-PGF2α, and TBARS were significantly increased in VHS compared with the normal salt group. CONCLUSION High dietary salt intake is associated with decreased nitric oxide mediated endothelium-dependent vasodilation in peripheral microcirculation and macrocirculation of healthy pregnant women due to increased oxidative stress.
Collapse
Affiliation(s)
- Martina Vulin
- Department of Gynaecology and Obstetrics, University Hospital Centre Osijek
- Department of Gynaecology and Obstetrics, Faculty of Medicine Osijek
| | - Andrijana Muller
- Department of Gynaecology and Obstetrics, University Hospital Centre Osijek
- Department of Gynaecology and Obstetrics, Faculty of Medicine Osijek
| | - Ines Drenjančević
- Department of Physiology and Immunology, Faculty of Medicine Osijek
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Petar Šušnjara
- Department of Physiology and Immunology, Faculty of Medicine Osijek
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Zrinka Mihaljević
- Department of Physiology and Immunology, Faculty of Medicine Osijek
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Ana Stupin
- Department of Physiology and Immunology, Faculty of Medicine Osijek
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| |
Collapse
|
|
9
|
Elijovich F, Kirabo A, Laffer CL. Salt Sensitivity of Blood Pressure in Black People: The Need to Sort Out Ancestry Versus Epigenetic Versus Social Determinants of Its Causation. Hypertension 2024; 81:456-467. [PMID: 37767696 PMCID: PMC10922075 DOI: 10.1161/hypertensionaha.123.17951] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
Race is a social construct, but self-identified Black people are known to have higher prevalence and worse outcomes of hypertension than White people. This may be partly due to the disproportionate incidence of salt sensitivity of blood pressure in Black people, a cardiovascular risk factor that is independent of blood pressure and has no proven therapy. We review the multiple physiological systems involved in regulation of blood pressure, discuss what, if anything is known about the differences between Black and White people in these systems and how they affect salt sensitivity of blood pressure. The contributions of genetics, epigenetics, environment, and social determinants of health are briefly touched on, with the hope of stimulating further work in the field.
Collapse
Affiliation(s)
- Fernando Elijovich
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Annet Kirabo
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Cheryl L Laffer
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN
| |
Collapse
|
|
10
|
Ramos-Gonzalez M, Smiljanec K, Mbakwe AU, Lobene AJ, Pohlig RT, Farquhar WB, Lennon SL. Sex influences blood pressure but not blood pressure variability in response to dietary sodium and potassium in salt-resistant adults. J Hum Hypertens 2024; 38:62-69. [PMID: 37620414 DOI: 10.1038/s41371-023-00855-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/26/2023]
Abstract
Dietary sodium and potassium have been shown to affect blood pressure (BP) but their influence on BP variability (BPV) is less studied as is the influence of sex. The aim of this study was to compare 24 h BP and short-term BPV in response to varying dietary levels of sodium and potassium in healthy non-obese normotensive salt-resistant adults. We hypothesized that high sodium would increase short-term BP and BPV while the addition of high potassium would counteract this increase. Furthermore, we hypothesized that women would experience greater increases in BPV under high sodium conditions compared to men while potassium would attenuate this response. Thirty-seven participants (17 M/20 W; 27 ± 5 years old; BMI 24.3 ± 3 kg/m2) completed seven days each of the following randomized diets: moderate potassium/low sodium (MK/LS), moderate potassium/high sodium (MK/HS) and high potassium/high sodium (HK/HS). BP and short-term BPV were assessed using 24 h ambulatory BP monitoring starting on day 6. BPV was calculated using the average real variability (ARV) index. Twenty-four hour, daytime, and nighttime systolic BP (SBP) were lower in women compared to men regardless of diet. However, 24 h and daytime SBP were lowered in women on the HK/HS diet compared to the MK/HS diet. There were no significant effects of diet or sex for 24 h, daytime or nighttime SBP ARV. However, men exhibited a higher 24 hDBP ARV than women regardless of diet. In conclusion, a high potassium diet lowered BP under high sodium conditions in women alone while men exhibited higher short-term BPV that was not influenced by diet.
Collapse
Affiliation(s)
| | - Katarina Smiljanec
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - Alexis U Mbakwe
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - Andrea J Lobene
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - Ryan T Pohlig
- Biostatistics Core Facility, University of Delaware, Newark, DE, USA
- Epidemiology Program, University of Delaware, Newark, DE, USA
| | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - Shannon L Lennon
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA.
| |
Collapse
|
|
11
|
Jeong S, Hunter SD, Cook MD, Grosicki GJ, Robinson AT. Salty Subjects: Unpacking Racial Differences in Salt-Sensitive Hypertension. Curr Hypertens Rep 2024; 26:43-58. [PMID: 37878224 PMCID: PMC11414742 DOI: 10.1007/s11906-023-01275-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2023] [Indexed: 10/26/2023]
Abstract
PURPOSE OF REVIEW To review underlying mechanisms and environmental factors that may influence racial disparities in the development of salt-sensitive blood pressure. RECENT FINDINGS Our group and others have observed racial differences in diet and hydration, which may influence salt sensitivity. Dietary salt elicits negative alterations to the gut microbiota and immune system, which may increase hypertension risk, but little is known regarding potential racial differences in these physiological responses. Antioxidant supplementation and exercise offset vascular dysfunction following dietary salt, including in Black adults. Furthermore, recent work proposes the role of racial differences in exposure to social determinants of health, and differences in health behaviors that may influence risk of salt sensitivity. Physiological and environmental factors contribute to the mechanisms that manifest in racial differences in salt-sensitive blood pressure. Using this information, additional work is needed to develop strategies that can attenuate racial disparities in salt-sensitive blood pressure.
Collapse
Affiliation(s)
- Soolim Jeong
- Neurovascular Physiology Laboratory (NVPL), School of Kinesiology, Auburn University, Auburn, AL, 36849, USA
| | - Stacy D Hunter
- Department of Health & Human Performance, Texas State University, San Marcos, TX, 78666, USA
| | - Marc D Cook
- Department of Kinesiology, North Carolina Agriculture and Technology State University, Greensboro, NC, 27411, USA
| | - Gregory J Grosicki
- Biodynamics and Human Performance Center, Georgia Southern University (Armstrong Campus), Savannah, GA, 31419, USA
| | - Austin T Robinson
- Neurovascular Physiology Laboratory (NVPL), School of Kinesiology, Auburn University, Auburn, AL, 36849, USA.
| |
Collapse
|
|
12
|
Fu Q, Chen R, Ding Y, Xu S, Huang C, He B, Jiang T, Zeng B, Bao M, Li S. Sodium intake and the risk of various types of cardiovascular diseases: a Mendelian randomization study. Front Nutr 2023; 10:1250509. [PMID: 38188872 PMCID: PMC10771828 DOI: 10.3389/fnut.2023.1250509] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 11/27/2023] [Indexed: 01/09/2024] Open
Abstract
Background The existing literature on the link between sodium intake and cardiovascular disease (CVD) largely consists of observational studies that have yielded inconsistent conclusions. In this study, our objective is to assess the causal relationship between sodium intake and 50 CVDs using two-sample Mendelian randomization (MR) analysis. Methods MR analyses were performed to investigate the associations between urinary sodium/creatinine ratio (UNa/UCr), an indicator of sodium intake, and 50 CVDs. The genome-wide association study (GWAS) for UNa/UCr was from the UK Biobank (UKBB), and the GWASs for CVDs were from FinnGen. A false discovery rate (FDR) threshold of 5% was applied for multiple comparison correction. Results The inverse-variance weighted method indicated that the genetically predicted UNa/UCr was significantly associated with 7 of 50 CVDs, including "Coronary atherosclerosis" (OR = 2.01; 95% CI: 1.37, 2.95), "Diseases of arteries, arterioles and capillaries" (OR = 1.88; 95% CI: 1.20, 2.94), "Hard cardiovascular diseases" (OR = 1.71; 95% CI: 1.24, 2.35), "Ischemic heart diseases" (OR = 2.06; 95% CI: 1.46, 2.93), "Major coronary heart disease event" (OR = 1.99; 95% CI: 1.36, 2.91), "Myocardial infarction" (OR = 2.03; 95% CI: 1.29, 3.19), and "Peripheral artery disease" (OR = 2.50; 95% CI: 1.35, 4.63). Similar results were obtained with the MR-Egger and weighted median methods. No significant heterogeneity or horizontal pleiotropy was found in this analysis. Conclusion Our study has uncovered a significant positive causal relationship between UNa/UCr and various CVDs. These results offer a new theoretical foundation for advocating the restriction of sodium intake as a preventive measure against CVD.
Collapse
Affiliation(s)
- Qingming Fu
- School of Stomatology, Changsha Medical University, Changsha, China
| | - Rumeng Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yining Ding
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Shuling Xu
- The Second Affiliated Hospital of Anhui Medical University, Heifei, China
| | - Chunxia Huang
- School of Stomatology, Changsha Medical University, Changsha, China
| | - Binsheng He
- The Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha, China
| | - Ting Jiang
- School of Stomatology, Changsha Medical University, Changsha, China
| | - Bin Zeng
- School of Stomatology, Changsha Medical University, Changsha, China
| | - Meihua Bao
- The Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha, China
- Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China
| | - Sen Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
|
13
|
Ramos Gonzalez M, Axler MR, Kaseman KE, Lobene AJ, Farquhar WB, Witman MA, Kirkman DL, Lennon SL. Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet. Physiol Rep 2023; 11:e15896. [PMID: 38110301 PMCID: PMC10727961 DOI: 10.14814/phy2.15896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 11/03/2023] [Accepted: 11/24/2023] [Indexed: 12/20/2023] Open
Abstract
High sodium diets (HSD) can cause vascular dysfunction, in part due to increases in reactive oxygen species (ROS). Melatonin reduces ROS in healthy and clinical populations and may improve vascular function. The purpose was to determine the effect of melatonin supplementation on vascular function and ROS during 10 days of a HSD. We hypothesized that melatonin supplementation during a HSD would improve vascular function and decrease ROS levels compared to HSD alone. Twenty-seven participants (13 M/14 W, 26.7 ± 2.9 years, BMI: 23.6 ± 2.0 kg/m2 , BP: 110 ± 9/67 ± 7 mmHg) were randomized to a 10-day HSD (6900 mg sodium/d) supplemented with either 10 mg of melatonin (HSD + MEL) or a placebo (HSD + PL) daily. Brachial artery flow-mediated dilation, a measure of macrovascular function, (HSD + PL: 7.1 ± 3.8%; HSD + MEL: 6.7 ± 3.4%; p = 0.59) and tissue oxygenation index (TSI) reperfusion rate, a measure of microvascular reactivity, (HSD + PL: 0.21 ± 0.06%/s; HSD + MEL: 0.21 ± 0.08%/s; p = 0.97) and TSI area under the curve (HSD + PL: 199899 ± 10,863 a.u.; HSD + MEL: 20315 ± 11,348 a.u.; p = 0.17) were similar at the end of each condition. Neither nitroxide molarity (HSD + PL: 7.8 × 10-5 ± 4.1 × 10-5 mol/L; HSD + MEL: 8.7 × 10-5 ± 5.1 × 10-5 mol/L; p = 0.55) nor free radical number (HSD + PL: 8.0 × 1015 ± 4.4 × 1015 ; HSD + MEL: 9.0 × 1015 ± 4.9 × 1015 ; p = 0.51) were different between conditions. Melatonin supplementation did not alter vascular function or ROS levels while on a HSD in this sample of young healthy normotensive adults.
Collapse
Affiliation(s)
| | - Michael R. Axler
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Kathryn E. Kaseman
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Andrea J. Lobene
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - William B. Farquhar
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Melissa A. Witman
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| | - Danielle L. Kirkman
- Department of Kinesiology and Health SciencesVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Shannon L. Lennon
- Department of Kinesiology and Applied PhysiologyUniversity of DelawareNewarkDelawareUSA
| |
Collapse
|
|
14
|
Vlachovsky SG, Di Ciano LA, Oddo EM, Azurmendi PJ, Silberstein C, Ibarra FR. Role of Female Sex Hormones and Immune Response in Salt-Sensitive Hypertension Development: Evidence from Experimental Models. Curr Hypertens Rep 2023; 25:405-419. [PMID: 37676461 DOI: 10.1007/s11906-023-01257-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2023] [Indexed: 09/08/2023]
Abstract
PURPOSEOF REVIEW Female sex hormones have systemic effects unrelated to their reproductive function. We describe experiences of different research groups and our own, on aspects related to the importance of female sex hormones on blood pressure (BP) regulation and salt-sensitivity-mediated BP response and salt sensitivity without alterations in BP, as well as renal sodium handling and interactions with the immune system. RECENT FINDINGS Changes in sodium intake in normotensive premenopausal women cause more BP variations than in men. After menopause, women often develop arterial hypertension (HT) with a profile of sodium sensitivity. Besides, experimental results have shown that in adult rat models resembling the postmenopausal hormonal state induced by ovariectomy, controlling BP is not enough to avoid renal and other tissue infiltration with immune cells, which does not occur when sodium intake is low or normal. Therefore, excess sodium promotes an inflammatory state with the involvement of immune cells. The evidence of activation of adaptive immunity, besides changes in T cell subpopulations, includes changes in sodium transporters and receptors. More studies are needed to evaluate the particular sodium sensitivity of women and its meaning. Changes in lifestyle and sodium intake reduction are the main therapeutic steps. However, to face the actual burden of salt-sensitive HT in postmenopausal women and its associated inflammatory/immune changes, it seems reasonable to work on immune cell activity by considering the peripheral blood mononuclear cell phenotypes of molecules and transport proteins related to sodium handle, both to screen for and treat cell activation.
Collapse
Affiliation(s)
- Sandra G Vlachovsky
- Universidad de Buenos Aires, Instituto de Investigaciones Medicas A. Lanari, Laboratorio de Nefrología Experimental y Bioquímica Molecular, Combatientes de Malvinas 3150, Buenos Aires, 1427, Argentina
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina
| | - Luis A Di Ciano
- Universidad de Buenos Aires, Instituto de Investigaciones Medicas A. Lanari, Laboratorio de Nefrología Experimental y Bioquímica Molecular, Combatientes de Malvinas 3150, Buenos Aires, 1427, Argentina
| | - Elisabet M Oddo
- Universidad de Buenos Aires, Instituto de Investigaciones Medicas A. Lanari, Laboratorio de Nefrología Experimental y Bioquímica Molecular, Combatientes de Malvinas 3150, Buenos Aires, 1427, Argentina
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina
| | - Pablo J Azurmendi
- Universidad de Buenos Aires, Instituto de Investigaciones Medicas A. Lanari, Laboratorio de Nefrología Experimental y Bioquímica Molecular, Combatientes de Malvinas 3150, Buenos Aires, 1427, Argentina
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina
| | - Claudia Silberstein
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Departamento de Ciencias Fisiológicas. Instituto de Fisiología y Biofísica B. Houssay (IFIBIO-Houssay), Laboratorio de Fisiología Renal, Paraguay 2155, piso 4, Buenos Aires, 1121, Argentina.
| | - Fernando R Ibarra
- Universidad de Buenos Aires, Instituto de Investigaciones Medicas A. Lanari, Laboratorio de Nefrología Experimental y Bioquímica Molecular, Combatientes de Malvinas 3150, Buenos Aires, 1427, Argentina.
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina.
- Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Departamento de Ciencias Fisiológicas. Instituto de Fisiología y Biofísica B. Houssay (IFIBIO-Houssay), Laboratorio de Fisiología Renal, Paraguay 2155, piso 4, Buenos Aires, 1121, Argentina.
| |
Collapse
|
|
15
|
Peprah E, Amegbor P, Laar A, Akasoe B, Commodore-Mensah Y. Reducing Dietary Sodium Intake among Young Adults in Ghana: A Call to Action. Nutrients 2023; 15:3562. [PMID: 37630752 PMCID: PMC10458370 DOI: 10.3390/nu15163562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/25/2023] [Accepted: 08/02/2023] [Indexed: 08/27/2023] Open
Abstract
The positive association between excessive dietary sodium intake, hypertension, and cardiovascular disease (CVD) has been widely investigated in observational studies and clinical trials. Reducing sodium intake is a proven strategy to prevent hypertension and the onset of CVD, a major cause of morbidity and mortality globally. Africa has the youngest population globally, which is key to the continent's sustainable development. However, in Africa, the epidemics of hypertension and CVD negatively impact life expectancy and economic growth. Ghana, like other African countries, is no exception. The factors contributing to the increasing burden of CVD and excessive sodium consumption are multi-faceted and multi-level, including individual lifestyle, neighborhood and built environments, and socio-economic and health policies. Thus, the implementation of evidence-based interventions such as the World Health Organization Best Buys that target the multi-level determinants of sodium consumption is urgently needed in Ghana and other African countries. The aim of this commentary is to highlight factors that contribute to excessive sodium consumption. Second, the commentary will showcase lessons of successful implementation of sodium reduction interventions in other countries. Such lessons may help avert CVD in young adults in Ghana and Africa.
Collapse
Affiliation(s)
- Emmanuel Peprah
- Department of Global and Environmental Health, NYU School of Global Public Health, 708 Broadway, New York, NY 10003, USA;
| | - Prince Amegbor
- Department of Global and Environmental Health, NYU School of Global Public Health, 708 Broadway, New York, NY 10003, USA;
| | - Amos Laar
- Department of Population, Family and Reproductive Health, School of Public Health, University of Ghana, Legon, Accra P.O. Box LG13, Ghana; (A.L.); (B.A.)
| | - Bismark Akasoe
- Department of Population, Family and Reproductive Health, School of Public Health, University of Ghana, Legon, Accra P.O. Box LG13, Ghana; (A.L.); (B.A.)
| | | |
Collapse
|
|
16
|
Watso JC, Fancher IS, Gomez DH, Hutchison ZJ, Gutiérrez OM, Robinson AT. The damaging duo: Obesity and excess dietary salt contribute to hypertension and cardiovascular disease. Obes Rev 2023; 24:e13589. [PMID: 37336641 PMCID: PMC10406397 DOI: 10.1111/obr.13589] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 05/08/2023] [Accepted: 05/24/2023] [Indexed: 06/21/2023]
Abstract
Hypertension is a primary risk factor for cardiovascular disease. Cardiovascular disease is the leading cause of death among adults worldwide. In this review, we focus on two of the most critical public health challenges that contribute to hypertension-obesity and excess dietary sodium from salt (i.e., sodium chloride). While the independent effects of these factors have been studied extensively, the interplay of obesity and excess salt overconsumption is not well understood. Here, we discuss both the independent and combined effects of excess obesity and dietary salt given their contributions to vascular dysfunction, autonomic cardiovascular dysregulation, kidney dysfunction, and insulin resistance. We discuss the role of ultra-processed foods-accounting for nearly 60% of energy intake in America-as a major contributor to both obesity and salt overconsumption. We highlight the influence of obesity on elevated blood pressure in the presence of a high-salt diet (i.e., salt sensitivity). Throughout the review, we highlight critical gaps in knowledge that should be filled to inform us of the prevention, management, treatment, and mitigation strategies for addressing these public health challenges.
Collapse
Affiliation(s)
- Joseph C. Watso
- Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, Florida, USA
| | - Ibra S. Fancher
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, USA
| | - Dulce H. Gomez
- School of Kinesiology, Auburn University, Auburn, Alabama, USA
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | | | - Orlando M. Gutiérrez
- Division of Nephrology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | | |
Collapse
|
|
17
|
Romberger NT, Stock JM, Patik JC, McMillan RK, Lennon SL, Edwards DG, Farquhar WB. Inverse salt sensitivity in normotensive adults: role of demographic factors. J Hypertens 2023; 41:934-940. [PMID: 36928305 PMCID: PMC10228636 DOI: 10.1097/hjh.0000000000003413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
BACKGROUND Salt sensitivity and inverse salt sensitivity [ISS; a reduction in blood pressure (BP) on a high sodium diet] are each associated with increased incidence of hypertension. The purpose of this analysis was to determine the prevalence of ISS in normotensive adults and whether ISS is associated with any demographic characteristic(s). METHODS Healthy normotensive, nonobese adults [ n = 84; 43 women; age = 37 ± 13 years; baseline mean arterial pressure (MAP) = 89 ± 8 mmHg] participated in a controlled feeding study, consuming 7-day low-sodium (20 mmol sodium/day) and high-sodium (300 mmol sodium/day) diets. Twenty-four-hour ambulatory BP was assessed on the last day of each diet. ISS was defined as a reduction in 24-h MAP more than 5 mmHg, salt sensitivity as an increase in MAP more than 5 mmHg and salt resistance as a change in MAP between -5 and 5 mmHg from low sodium to high sodium. RESULTS Using this cutoff, 10.7% were ISS, 76.2% salt resistant, and 13.1% salt sensitive. Prevalence of ISS was similar between sexes and age groups ( P > 0.05). However, ISS was more prevalent in those with normal BMI (15.8% ISS) compared with those with overweight BMI (0% ISS; P < 0.01). Interestingly, classification of participants using a salt sensitivity index (ΔMAP/Δ urinary sodium excretion) categorized 21.4% as ISS, 48.8% salt resistant, and 29.8% salt sensitive. CONCLUSION Overall, we found that the prevalence of ISS was 10.7% (5 mmHg cutoff) or 21.4% (salt sensitivity index), and that ISS was associated with lower BMI. These results highlight the importance of future work to understand the mechanisms of ISS and to standardize salt sensitivity assessment.
Collapse
Affiliation(s)
- Nathan T Romberger
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, USA
| | | | | | | | | | | | | |
Collapse
|
|
18
|
Tolj I, Stupin A, Drenjančević I, Šušnjara P, Perić L, Stupin M. The Role of Nitric Oxide in the Micro- and Macrovascular Response to a 7-Day High-Salt Diet in Healthy Individuals. Int J Mol Sci 2023; 24:ijms24087157. [PMID: 37108318 PMCID: PMC10138534 DOI: 10.3390/ijms24087157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/06/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
This study aimed to investigate the specific role of nitric oxide (NO) in micro- and macrovascular response to a 7-day high-salt (HS) diet, specifically by measuring skin microvascular local thermal hyperemia and the flow-mediated dilation of the brachial artery, as well as serum NO and three NO synthase enzyme (NOS) isoform concentrations in healthy individuals. It also aimed to examine the concept of non-osmotic sodium storage in the skin following the HS diet by measuring body fluid status and systemic hemodynamic responses, as well as serum vascular endothelial growth factor C (VEGF-C) concentration. Forty-six young, healthy individuals completed a 7-day low-salt diet, followed by a 7-day HS diet protocol. The 7-day HS diet resulted in impaired NO-mediated endothelial vasodilation in peripheral microcirculation and conduit arteries, in increased eNOS, decreased nNOS, and unchanged iNOS concentration and NO serum level. The HS diet did not change the volume of interstitial fluid, the systemic vascular resistance or the VEGF-C serum level. These results indicate that the 7-day HS-diet induces systemic impairment of NO-mediated endothelial vasodilation, while dissociation in the eNOS and nNOS response indicates complex adaptation of main NO-generating enzyme isoforms to HS intake in healthy individuals. Our results failed to support the concept of non-osmotic sodium storage.
Collapse
Affiliation(s)
- Ivana Tolj
- Department of Internal Medicine and History of Medicine, Faculty of Medicine Osijek, Josip Juraj University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
- Department of Nephrology, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia
| | - Ana Stupin
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Ines Drenjančević
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Petar Šušnjara
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Leon Perić
- Department of Emergency Medicine of Osijek-Baranja County, J. Huttlera 2, 31000 Osijek, Croatia
| | - Marko Stupin
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
- Department for Cardiovascular Disease, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia
| |
Collapse
|
|
19
|
Dunaway LS, Cook AK, Botta D, Molina PA, d’Uscio LV, Katusic ZS, Pollock DM, Inscho EW, Pollock JS. Endothelial Histone Deacetylase 1 Activity Impairs Kidney Microvascular NO Signaling in Rats fed a High Salt Diet. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.03.08.531731. [PMID: 36945391 PMCID: PMC10028933 DOI: 10.1101/2023.03.08.531731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
Aim We aimed to identify new mechanisms by which a high salt diet (HS) decreases NO production in kidney microvascular endothelial cells. Specifically, we hypothesized HS impairs NO signaling through a histone deacetylase 1 (HDAC1)-dependent mechanism. Methods Male Sprague Dawley rats were fed normal salt diet (NS; 0.49% NaCl) or high salt diet (4% NaCl) for two weeks. NO signaling was assessed by measuring L-NAME induced vasoconstriction of the afferent arteriole using the blood perfused juxtamedullary nephron (JMN) preparation. In this preparation, kidneys were perfused with blood from a donor rat on a matching or different diet to that of the kidney donor. Kidney endothelial cells were isolated with magnetic activated cell sorting and HDAC1 activity was measured. Results We found that HS impaired NO signaling in the afferent arteriole. This was restored by inhibition of HDAC1 with MS-275. Consistent with these findings, HDAC1 activity was increased in kidney endothelial cells. We further found the loss of NO to be dependent upon the diet of the blood donor rather than the diet of the kidney donor and the plasma from HS fed rats to be sufficient to induce dysfunction suggesting a humoral factor, we termed Plasma Derived Endothelial-dysfunction Mediator (PDEM), mediates the endothelial dysfunction. The antioxidants, PEG-SOD and PEG-catalase, as well as the NOS cofactor, tetrahydrobiopterin, restored NO signaling. Conclusion We conclude that HS activates endothelial HDAC1 through PDEM leading to decreased NO signaling. This study provides novel insights into the molecular mechanisms by which a HS decreases renal microvascular endothelial NO signaling.
Collapse
Affiliation(s)
- Luke S. Dunaway
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Anthony K. Cook
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Davide Botta
- Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Patrick A. Molina
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Livius V. d’Uscio
- Department of Anesthesiology and Pharmacology, Mayo Clinic, Rochester, MN USA
| | - Zvonimir S. Katusic
- Department of Anesthesiology and Pharmacology, Mayo Clinic, Rochester, MN USA
| | - David M. Pollock
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Edward W. Inscho
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| | - Jennifer S. Pollock
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL USA
| |
Collapse
|
|
20
|
Decker KP, Chiu A, Weggen JB, Richardson JW, Hogwood AC, Darling AM, Garten RS. High sodium intake differentially impacts brachial artery dilation when evaluated with reactive versus active hyperemia in salt resistant individuals. J Appl Physiol (1985) 2023; 134:277-287. [PMID: 36548512 DOI: 10.1152/japplphysiol.00461.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This study sought to determine if high sodium (HS) intake in salt resistant (SR) individuals attenuates upper limb arterial dilation in response to reactive (occlusion) and active (exercise) hyperemia, two stimuli with varying vasodilatory mechanisms, and the role of oxidative stress in this response. Ten young, SR participants (9 males, 1 female) consumed a 7-day HS (6,900 mg/day) and a 7-day recommended sodium intake (RI: 2,300 mg/day) diet in a randomized order. On the last day of each diet, brachial artery (BA) function was evaluated via reactive (RH-FMD: 5 min of cuff occlusion) and active [handgrip (HG) exercise] hyperemia after consumption of both placebo (PL) and antioxidants (AO). The HS diet significantly elevated sodium excretion (P < 0.05), but mean arterial blood pressure was unchanged. During the PL condition, the HS diet significantly reduced RH-FMD when compared with RI diet (P = 0.01), but this reduction was significantly restored (P = 0.01) when supplemented with AO (HS + PL: 5.9 ± 3.4; HS + AO: 8.2 ± 2.7; RI + PL: 8.9 ± 4.7; RI + AO: 7.0 ± 2.1%). BA shear-to-dilation slopes, evaluated across all HG exercise workloads, were not significantly different across sodium intervention or AO supplementation. In SR individuals, HS intake impaired BA function when assessed via RH-FMD, but was restored with acute AO consumption suggesting oxidative stress as a contributor to this dysfunction. However, exercise-induced BA dilation was unaltered, potentially implicating an inability of HS intake to influence the mechanisms responsible for effectively maintaining skeletal muscle perfusion during exercise.NEW & NOTEWORTHY This study examined if high sodium (HS) intake in salt resistant (SR) individuals attenuates brachial artery (BA) flow-mediated dilation in response to reactive (occlusion) and active (exercise) hyperemia. In SR individuals, HS intake impaired reactive hyperemia-induced BA dilation, but not exercise-induced BA dilation. This finding suggests that although brachial artery nitric oxide bioavailability may be reduced following HS intake, the redundant mechanisms associated with adequate upper limb blood flow regulation during exercise are maintained.
Collapse
Affiliation(s)
- Kevin P Decker
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware
| | - Alex Chiu
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia
| | - Jennifer B Weggen
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia
| | - Jacob W Richardson
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia
| | - Austin C Hogwood
- Department of Kinesiology, University of Virginia, Charlottesville, Virginia
| | - Ashley M Darling
- Department of Kinesiology, University of Texas at Arlington, Arlington, Texas
| | - Ryan S Garten
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia
| |
Collapse
|
|
21
|
Rossitto G, Delles C. Mechanisms of sodium-mediated injury in cardiovascular disease: old play, new scripts. FEBS J 2022; 289:7260-7273. [PMID: 34355504 DOI: 10.1111/febs.16155] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 06/08/2021] [Accepted: 08/04/2021] [Indexed: 01/13/2023]
Abstract
There is a strong association between salt intake and cardiovascular diseases, particularly hypertension, on the population level. The mechanisms that explain this association remain incompletely understood and appear to extend beyond blood pressure. In this review, we describe some of the 'novel' roles of Na+ in cardiovascular health and disease: energetic implications of sodium handling in the kidneys; local accumulation in tissue; fluid dynamics; and the role of the microvasculature, with particular focus on the lymphatic system. We describe the interplay between these factors that involves body composition, metabolic signatures, inflammation and composition of the extracellular and intracellular milieus.
Collapse
Affiliation(s)
- Giacomo Rossitto
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.,Department of Medicine (DIMED), University of Padua, Italy
| | - Christian Delles
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK
| |
Collapse
|
|
22
|
Kirkman DL, Ramick MG, Muth BJ, Stock JM, Townsend RR, Edwards DG. Sex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease. Am J Physiol Heart Circ Physiol 2022; 323:H1130-H1136. [PMID: 36269643 PMCID: PMC9678402 DOI: 10.1152/ajpheart.00500.2022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/30/2022] [Accepted: 10/19/2022] [Indexed: 12/14/2022]
Abstract
Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer's solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females.NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD.
Collapse
Affiliation(s)
- Danielle L Kirkman
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia
| | - Meghan G Ramick
- Department of Kinesiology, West Chester University, West Chester, Pennsylvania
| | - Bryce J Muth
- School of Health Sciences, Stockton University, Galloway Township, New Jersey
| | - Joseph M Stock
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware
| | - Raymond R Townsend
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - David G Edwards
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware
| |
Collapse
|
|
23
|
Lobene AJ, Smiljanec K, Axler MR, Ramos-Gonzalez M, Lennon SL. Greater adherence to healthy dietary patterns is associated with lower diastolic blood pressure and augmentation index in healthy, young adults. Nutr Res 2022; 106:60-71. [PMID: 36126530 PMCID: PMC10335482 DOI: 10.1016/j.nutres.2022.07.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 07/28/2022] [Accepted: 07/30/2022] [Indexed: 11/20/2022]
Abstract
More than two-thirds of cardiovascular disease (CVD) deaths worldwide are attributable to dietary factors. Blood pressure variability (BPV), endothelial dysfunction, and arterial stiffness are important CVD risk factors. Although studies show a link between consuming a healthy diet and lower BPV and stiffness and improved endothelial function, research in young, healthy adults is scarce. We hypothesized that, in young, healthy adults, diet quality would be inversely associated with BPV and arterial stiffness and positively associated with endothelial function. This cross-sectional study included 56 healthy young adults (34 women/22 men, age 26.7 ± 0.8 years, body mass index 23.4 ± 0.4 kg/m2, blood pressure [BP] 113/69 mmHg). Three-day diet records were used to calculate two Dietary Approaches to Stop Hypertension (DASH) diet scores, the alternative Mediterranean Diet (aMED) score, and the Healthy Eating Index-2015 (HEI-2015) based on the 2015-2020 Dietary Guidelines for Americans. Twenty-four-hour ambulatory BP data were used to calculate average real variability of systolic and diastolic BP. Endothelial function was assessed by flow-mediated dilation, and arterial stiffness was assessed by pulse wave velocity and augmentation index (AIx). Overall, the HEI-2015 was inversely associated with 24-hour diastolic BP (DBP) and daytime DBP, and the aMED score was inversely associated with AIx. In our exploratory analyses, the Fung DASH score was inversely associated with 24-hour DBP and daytime DBP in women, but not men. These findings suggest that consuming a diet that aligns with the DASH diet, the Mediterranean diet, and/or the 2015-2020 Dietary Guidelines for Americans is associated with cardiovascular benefits in healthy, young adults.
Collapse
Affiliation(s)
- Andrea J Lobene
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, 19713.
| | - Katarina Smiljanec
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, 19713.
| | - Michael R Axler
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, 19713.
| | - Macarena Ramos-Gonzalez
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, 19713.
| | - Shannon L Lennon
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, 19713.
| |
Collapse
|
|
24
|
Krajina I, Stupin A, Šola M, Mihalj M. Oxidative Stress Induced by High Salt Diet—Possible Implications for Development and Clinical Manifestation of Cutaneous Inflammation and Endothelial Dysfunction in Psoriasis vulgaris. Antioxidants (Basel) 2022; 11:antiox11071269. [PMID: 35883760 PMCID: PMC9311978 DOI: 10.3390/antiox11071269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/19/2022] [Accepted: 06/23/2022] [Indexed: 02/07/2023] Open
Abstract
Although oxidative stress is recognized as an important effector mechanism of the immune system, uncontrolled formation of reactive oxygen and nitrogen species promotes excessive tissue damage and leads to disease development. In view of this, increased dietary salt intake has been found to damage redox systems in the vessel wall, resulting in endothelial dysfunction associated with NO uncoupling, inflammation, vascular wall remodeling and, eventually, atherosclerosis. Several studies have reported increased systemic oxidative stress accompanied by reduced antioxidant capacity following a high salt diet. In addition, vigorous ionic effects on the immune mechanisms, such as (trans)differentiation of T lymphocytes are emerging, which together with the evidence of NaCl accumulation in certain tissues warrants a re-examination of the data derived from in vitro research, in which the ionic influence was excluded. Psoriasis vulgaris (PV), as a primarily Th17-driven inflammatory skin disease with proven inflammation-induced accumulation of sodium chloride in the skin, merits our interest in the role of oxidative stress in the pathogenesis of PV, as well as in the possible beneficial effects that could be achieved through modulation of dietary salt intake and antioxidant supplementation.
Collapse
Affiliation(s)
- Ivana Krajina
- Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia;
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Ana Stupin
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia;
- Institute and Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Marija Šola
- Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia;
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
- Correspondence: (M.Š.); (M.M.); Tel.: +385-31-512-800 (M.M.)
| | - Martina Mihalj
- Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia;
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, HR-31000 Osijek, Croatia;
- Institute and Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
- Correspondence: (M.Š.); (M.M.); Tel.: +385-31-512-800 (M.M.)
| |
Collapse
|
|
25
|
Stock JM, Chelimsky G, Edwards DG, Farquhar WB. Dietary sodium and health: How much is too much for those with orthostatic disorders? Auton Neurosci 2022; 238:102947. [PMID: 35131651 PMCID: PMC9296699 DOI: 10.1016/j.autneu.2022.102947] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 11/09/2021] [Accepted: 01/16/2022] [Indexed: 10/19/2022]
Abstract
High dietary salt (NaCl) increases blood pressure (BP) and can adversely impact multiple target organs including the vasculature, heart, kidneys, brain, autonomic nervous system, skin, eyes, and bone. However, patients with orthostatic disorders are told to increase their NaCl intake to help alleviate symptoms. While there is evidence to support the short-term benefits of increasing NaCl intake in these patients, there are few studies assessing the benefits and side effects of long-term high dietary NaCl. The evidence reviewed suggests that high NaCl can adversely impact multiple target organs, often independent of BP. However, few of these studies have been performed in patients with orthostatic disorders. We conclude that the recommendation to increase dietary NaCl in patients with orthostatic disorders should be done with care, keeping in mind the adverse impact on dietary NaCl in people without orthostatic disorders. Modest, rather than robust, increases in NaCl intake may be sufficient to alleviate symptoms but also minimize any long-term negative effects.
Collapse
Affiliation(s)
- Joseph M Stock
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Gisela Chelimsky
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States of America
| | - David G Edwards
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America.
| |
Collapse
|
|
26
|
Role of Oxidative Stress in Vascular Low-Grade Inflammation Initiation Due to Acute Salt Loading in Young Healthy Individuals. Antioxidants (Basel) 2022; 11:antiox11030444. [PMID: 35326095 PMCID: PMC8944840 DOI: 10.3390/antiox11030444] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/20/2022] [Accepted: 02/21/2022] [Indexed: 02/01/2023] Open
Abstract
This study aimed to investigate the effect of 7-day high-salt (HS) and the specific role of oxidative stress on vascular low-grade inflammation initiation in young salt-resistant healthy individuals. 30 young healthy individuals adhered to a 7-day low-salt (LS) diet (3.5 g salt/day), followed by a 7-day high-salt (HS) diet (~14.7 g salt/day) protocol. Pro- and anti-inflammatory cytokines, frequencies of peripheral blood Th17 and Treg cells, Th17/Treg ratio, enzymes SGK1, and p38/MAP kinase, as well as biomarkers of endothelial activation and oxidative stress, were measured before and after the 7-day HS diet protocol. Short-term HS diet significantly increased serum level of pro-inflammatory cytokines INF-γ, TNF-α, IL-9, and IL-17A levels, but also of anti-inflammatory cytokines IL-10 and TGF-β1. Relative amount of total SGK1 significantly increased, following the 7-day HS diet. Increased oxidative stress level, following HS diet, was negatively associated with the frequency of Treg cells. The increase in relative amount of total SGK1 in peripheral mononuclear cells following 7-day HS diet suggests lymphocyte (re)activation, in response to HS intake, resulting in enhanced production of pro-inflammatory (IL-17, INF-γ), but also anti-inflammatory cytokines (IL-10 and TGF-β1). Increased oxidative stress, due to HS loading, alters immune regulatory mechanisms, presumably via effects on Treg cells.
Collapse
|
|
27
|
Zeng C, Rosenberg L, Li X, Djousse L, Wei J, Lei G, Zhang Y. OUP accepted manuscript. Eur Heart J 2022; 43:1743-1755. [PMID: 35201347 PMCID: PMC9076395 DOI: 10.1093/eurheartj/ehac059] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 10/19/2021] [Accepted: 01/27/2022] [Indexed: 11/17/2022] Open
Abstract
Aims Previous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among individuals with hypertension; findings on the effect of intake among individuals without hypertension have been equivocal. We aimed to compare the risks of incident CVD and all-cause mortality among initiators of sodium-containing acetaminophen with the risk of initiators of non-sodium-containing formulations of the same drug according to the history of hypertension. Methods and results Using The Health Improvement Network, we conducted two cohort studies among individuals with and without hypertension. We examined the relation of sodium-containing acetaminophen to the risk of each outcome during 1-year follow-up using marginal structural models with an inverse probability weighting to adjust for time-varying confounders. The outcomes were incident CVD (myocardial infarction, stroke, and heart failure) and all-cause mortality. Among individuals with hypertension (mean age: 73.4 years), 122 CVDs occurred among 4532 initiators of sodium-containing acetaminophen (1-year risk: 5.6%) and 3051 among 146 866 non-sodium-containing acetaminophen initiators (1-year risk: 4.6%). The average weighted hazard ratio (HR) was 1.59 [95% confidence interval (CI) 1.32–1.92]. Among individuals without hypertension (mean age: 71.0 years), 105 CVDs occurred among 5351 initiators of sodium-containing acetaminophen (1-year risk: 4.4%) and 2079 among 141 948 non-sodium-containing acetaminophen initiators (1-year risk: 3.7%), with an average weighted HR of 1.45 (95% CI 1.18–1.79). Results of specific CVD outcomes and all-cause mortality were similar. Conclusion The initiation of sodium-containing acetaminophen was associated with increased risks of CVD and all-cause mortality among individuals with or without hypertension. Our findings suggest that individuals should avoid unnecessary excessive sodium intake through sodium-containing acetaminophen use.
Collapse
Affiliation(s)
- Chao Zeng
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Lynn Rosenberg
- Slone Epidemiology Center at Boston University, Boston, MA, USA
| | - Xiaoxiao Li
- Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China
| | - Luc Djousse
- Division of Aging, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Jie Wei
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Health Management Center, Xiangya Hospital, Central South University, Changsha, China
| | | | | |
Collapse
|
|
28
|
Sodium Intake as a Cardiovascular Risk Factor: A Narrative Review. Nutrients 2021; 13:nu13093177. [PMID: 34579054 PMCID: PMC8470268 DOI: 10.3390/nu13093177] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/05/2021] [Accepted: 09/10/2021] [Indexed: 01/11/2023] Open
Abstract
While sodium is essential for human homeostasis, current salt consumption far exceeds physiological needs. Strong evidence suggests a direct causal relationship between sodium intake and blood pressure (BP) and a modest reduction in salt consumption is associated with a meaningful reduction in BP in hypertensive as well as normotensive individuals. Moreover, while long-term randomized controlled trials are still lacking, it is reasonable to assume a direct relationship between sodium intake and cardiovascular outcomes. However, a consensus has yet to be reached on the effectiveness, safety and feasibility of sodium intake reduction on an individual level. Beyond indirect BP-mediated effects, detrimental consequences of high sodium intake are manifold and pathways involving vascular damage, oxidative stress, hormonal alterations, the immune system and the gut microbiome have been described. Globally, while individual response to salt intake is variable, sodium should be perceived as a cardiovascular risk factor when consumed in excess. Reduction of sodium intake on a population level thus presents a potential strategy to reduce the burden of cardiovascular disease worldwide. In this review, we provide an update on the consequences of salt intake on human health, focusing on BP and cardiovascular outcomes as well as underlying pathophysiological hypotheses.
Collapse
|
|
29
|
Migdal KU, Robinson AT, Watso JC, Babcock MC, Lennon SL, Martens CR, Serrador JM, Farquhar WB. A high salt meal does not impair cerebrovascular reactivity in healthy young adults. Physiol Rep 2021; 8:e14585. [PMID: 33038066 PMCID: PMC7547584 DOI: 10.14814/phy2.14585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 01/11/2023] Open
Abstract
A high sodium (Na+) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty‐seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross‐over study. Participants were given a low Na+ meal (LSM; 138 mg Na+) and a high Na+ meal (HSM; 1,495 mg Na+) separated by ≥ one week. Serum Na+, beat‐to‐beat BP, middle cerebral artery velocity (transcranial Doppler), and end‐tidal carbon dioxide (PETCO2) were measured pre‐ (baseline) and 60 min post‐prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow‐mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p < .01). Cerebrovascular reactivity to hypercapnia (meal effect: p = .41) and to hypocapnia (meal effect: p = .65) were not affected by the HSM. Contrary with previous findings, FMD was not reduced following the HSM (meal effect: p = .74). These data suggest that a single high Na+ meal does not acutely impair cerebrovascular reactivity, and suggests that despite prior findings, a single high Na+ meal does not impair peripheral vascular function in healthy adults.
Collapse
Affiliation(s)
- Kamila U Migdal
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Austin T Robinson
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Joseph C Watso
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Matthew C Babcock
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Shannon L Lennon
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Christopher R Martens
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| | - Jorge M Serrador
- Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - William B Farquhar
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, USA
| |
Collapse
|
|
30
|
Migdal KU, Robinson AT, Watso JC, Babcock MC, Lennon SL, Martens CR, Serrador JM, Farquhar WB. Ten days of high dietary sodium does not impair cerebral blood flow regulation in healthy adults. Auton Neurosci 2021; 234:102826. [PMID: 34058717 DOI: 10.1016/j.autneu.2021.102826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 03/19/2021] [Accepted: 05/14/2021] [Indexed: 10/21/2022]
Abstract
High dietary sodium impairs cerebral blood flow regulation in rodents and is associated with increased stroke risk in humans. However, the effects of multiple days of high dietary sodium on cerebral blood flow regulation in humans is unknown. Therefore, the purpose of this study was to determine whether ten days of high dietary sodium impairs cerebral blood flow regulation. Ten participants (3F/7M; age: 30 ± 10 years; blood pressure (BP): 113 ± 8/62 ± 9 mmHg) participated in this randomized, cross-over design study. Participants were placed on 10-day diets that included either low- (1000 mg/d), medium- (2300 mg/d) or high- (7000 mg/d) sodium separated by ≥four weeks. Urinary sodium excretion, beat-to-beat BP (finger photoplethysmography), middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (capnography) was measured. Dynamic cerebral autoregulation during a ten-minute baseline was calculated and cerebrovascular reactivity assessed by determining the percent change in middle cerebral artery blood flow velocity to hypercapnia (8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Urinary sodium excretion increased in a stepwise manner (ANOVA P = 0.001) from the low, to medium, to high condition. There were no differences in dynamic cerebral autoregulation between conditions. While there was a trend for a difference during cerebrovascular reactivity to hypercapnia (ANOVA P = 0.06), this trend was abolished when calculating cerebrovascular conductance (ANOVA: P = 0.28). There were no differences in cerebrovascular reactivity (ANOVA P = 0.57) or conductance (ANOVA: P = 0.73) during hypocapnia. These data suggest that ten days of a high sodium diet does not impair cerebral blood flow regulation in healthy adults.
Collapse
Affiliation(s)
- Kamila U Migdal
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Austin T Robinson
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America; School of Kinesiology, Auburn University, Auburn, AL, United States of America
| | - Joseph C Watso
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Matthew C Babcock
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Shannon L Lennon
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Christopher R Martens
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Jorge M Serrador
- Department of Pharmacology, Physiology & Neuroscience, Rutgers University, Newark, NJ, United States of America
| | - William B Farquhar
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, DE, United States of America.
| |
Collapse
|
|
31
|
Is There Association between Altered Adrenergic System Activity and Microvascular Endothelial Dysfunction Induced by a 7-Day High Salt Intake in Young Healthy Individuals. Nutrients 2021; 13:nu13051731. [PMID: 34065261 PMCID: PMC8161165 DOI: 10.3390/nu13051731] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/12/2021] [Accepted: 05/18/2021] [Indexed: 01/06/2023] Open
Abstract
This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines’ level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.
Collapse
|
|
32
|
Genovesi S, Giussani M, Orlando A, Orgiu F, Parati G. Salt and Sugar: Two Enemies of Healthy Blood Pressure in Children. Nutrients 2021; 13:697. [PMID: 33671538 PMCID: PMC7927006 DOI: 10.3390/nu13020697] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/07/2021] [Accepted: 02/19/2021] [Indexed: 02/06/2023] Open
Abstract
The prevalence of essential arterial hypertension in children and adolescents has grown considerably in the last few decades, making this disease a major clinical problem in the pediatric age. The pathogenesis of arterial hypertension is multifactorial, with one of the components being represented by incorrect eating habits. In particular, excessive salt and sugar intake can contribute to the onset of hypertension in children, particularly in subjects with excess weight. Babies have an innate predisposition for sweet taste, while that for salty taste manifests after a few weeks. The recent modification of dietary styles and the current very wide availability of salt and sugar has led to an exponential increase in the consumption of these two nutrients. The dietary intake of salt and sugar in children is in fact much higher than that recommended by health agencies. The purpose of this review is to explore the mechanisms via which an excessive dietary intake of salt and sugar can contribute to the onset of arterial hypertension in children and to show the most important clinical studies that demonstrate the association between these two nutrients and arterial hypertension in pediatric age. Correct eating habits are essential for the prevention and nondrug treatment of essential hypertension in children and adolescents.
Collapse
Affiliation(s)
- Simonetta Genovesi
- School of Medicine and Surgery, University of Milano-Bicocca, 20100 Milan, Italy; (F.O.); (G.P.)
- Istituto Auxologico Italiano, IRCCS, Cardiology Unit, 20100 Milan, Italy;
| | - Marco Giussani
- Family Pediatrician, Agenzia Tutela Salute, 20100 Milan, Italy;
| | - Antonina Orlando
- Istituto Auxologico Italiano, IRCCS, Cardiology Unit, 20100 Milan, Italy;
| | - Francesca Orgiu
- School of Medicine and Surgery, University of Milano-Bicocca, 20100 Milan, Italy; (F.O.); (G.P.)
| | - Gianfranco Parati
- School of Medicine and Surgery, University of Milano-Bicocca, 20100 Milan, Italy; (F.O.); (G.P.)
- Istituto Auxologico Italiano, IRCCS, Cardiology Unit, 20100 Milan, Italy;
| |
Collapse
|
|
33
|
Mechanisms of Dietary Sodium-Induced Impairments in Endothelial Function and Potential Countermeasures. Nutrients 2021; 13:nu13010270. [PMID: 33477837 PMCID: PMC7832854 DOI: 10.3390/nu13010270] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/13/2021] [Accepted: 01/16/2021] [Indexed: 01/11/2023] Open
Abstract
Despite decades of efforts to reduce sodium intake, excess dietary sodium remains commonplace, and contributes to increased cardiovascular morbidity and mortality independent of its effects on blood pressure. An increasing amount of research suggests that high-sodium diets lead to reduced nitric oxide-mediated endothelial function, even in the absence of a change in blood pressure. As endothelial dysfunction is an early step in the progression of cardiovascular diseases, the endothelium presents a target for interventions aimed at reducing the impact of excess dietary sodium. In this review, we briefly define endothelial function and present the literature demonstrating that excess dietary sodium results in impaired endothelial function. We then discuss the mechanisms through which sodium impairs the endothelium, including increased reactive oxygen species, decreased intrinsic antioxidant defenses, endothelial cell stiffening, and damage to the endothelial glycocalyx. Finally, we present selected research findings suggesting that aerobic exercise or increased intake of dietary potassium may counteract the deleterious vascular effects of a high-sodium diet.
Collapse
|
|
34
|
Wang Y, Zhang J, Wier WG, Chen L, Blaustein MP. NO-induced vasodilation correlates directly with BP in smooth muscle-Na/Ca exchanger-1-engineered mice: elevated BP does not attenuate endothelial function. Am J Physiol Heart Circ Physiol 2021; 320:H221-H237. [PMID: 33124883 PMCID: PMC7847073 DOI: 10.1152/ajpheart.00487.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/26/2020] [Accepted: 10/26/2020] [Indexed: 12/29/2022]
Abstract
Arterial smooth muscle Na+/Ca2+ exchanger-1 (SM-NCX1) promotes vasoconstriction or vasodilation by mediating, respectively, Ca2+ influx or efflux. In vivo, SM-NCX1 mediates net Ca2+ influx to help maintain myogenic tone (MT) and neuronally activated constriction. SM-NCX1-TG (overexpressing transgenic) mice have increased MT and mean blood pressure (MBP; +13.5 mmHg); SM-NCX1-KO (knockout) mice have reduced MT and MBP (-11.1 mmHg). Endothelium-dependent vasodilation (EDV) is often impaired in hypertension. We tested whether genetically engineered SM-NCX1 expression and consequent BP changes similarly alter EDV. Isolated, pressurized mesenteric resistance arteries with MT from SM-NCX1-TG and conditional SM-NCX1-KO mice, and femoral arteries in vivo from TG mice were studied. Acetylcholine (ACh)-dilated TG arteries with MT slightly more than control or KO arteries, implying that SM-NCX1 overexpression does not impair EDV. In preconstricted KO, but not TG mouse arteries, however, ACh- and bradykinin-triggered vasodilation was markedly attenuated. To circumvent the endothelium, phenylephrine-constricted resistance arteries were tested with Na-nitroprusside [SNP; nitric oxide (NO) donor] and cGMP. This endothelium-independent vasodilation was augmented in TG but attenuated in KO arteries that lack NCX1-mediated Ca2+ clearance. Baseline cytosolic Ca2+ ([Ca2+]cyt) was elevated in TG femoral arteries in vivo, supporting the high BP; furthermore, SNP-triggered [Ca2+]cyt decline and vasodilation were augmented as NO and cGMP promote myocyte polarization thereby enhancing NCX1-mediated Ca2+ efflux. The TG mouse data indicate that BP elevation does not attenuate endothelium-dependent vasodilation. Thus, in essential hypertension and many models the endothelial impairment that supports the hypertension apparently is not triggered by BP elevation but by extravascular mechanisms.NEW & NOTEWORTHY Endothelium-dependent, ACh-induced vasodilation (EDV) is attenuated, and arterial myocyte Na+/Ca2+ exchangers (NCX1) are upregulated in many forms of hypertension. Surprisingly, mildly hypertensive smooth muscle-specific (SM)-NCX1 transgenic mice exhibited modestly enhanced EDV and augmented endothelium-independent vasodilation (EIV). Conversely, mildly hypotensive SM-NCX1-knockout mice had greatly attenuated EIV. These adaptations help compensate for NCX1 expression-induced alterations in cytosolic Ca2+ and blood pressure (BP) and belie the view that elevated BP, itself, causes the endothelial dysregulation in hypertension.
Collapse
Affiliation(s)
- Youhua Wang
- Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
- Department of Physical Education, Shaanxi Normal University, Xi'an, Shaanxi, China
| | - Jin Zhang
- Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
| | - W Gil Wier
- Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Ling Chen
- Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Mordecai P Blaustein
- Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
35
|
Silva-Couto S, Correia-Santos AM, Vicente GC, Castro CLC, Barreto VDLM, Martins JEC, Lenzi Q, Boaventura GT, Chagas MA. Maternal Intake of Flaxseed During Lactation and Exercise Training Protect Against Salt Overload-Induced Aortic Remodeling in Adult Offspring. INTERNATIONAL JOURNAL OF CARDIOVASCULAR SCIENCES 2020. [DOI: 10.36660/ijcs.20190165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
|
|
36
|
Valenzuela PL, Carrera-Bastos P, Gálvez BG, Ruiz-Hurtado G, Ordovas JM, Ruilope LM, Lucia A. Lifestyle interventions for the prevention and treatment of hypertension. Nat Rev Cardiol 2020; 18:251-275. [PMID: 33037326 DOI: 10.1038/s41569-020-00437-9] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/24/2020] [Indexed: 02/07/2023]
Abstract
Hypertension affects approximately one third of the world's adult population and is a major cause of premature death despite considerable advances in pharmacological treatments. Growing evidence supports the use of lifestyle interventions for the prevention and adjuvant treatment of hypertension. In this Review, we provide a summary of the epidemiological research supporting the preventive and antihypertensive effects of major lifestyle interventions (regular physical exercise, body weight management and healthy dietary patterns), as well as other less traditional recommendations such as stress management and the promotion of adequate sleep patterns coupled with circadian entrainment. We also discuss the physiological mechanisms underlying the beneficial effects of these lifestyle interventions on hypertension, which include not only the prevention of traditional risk factors (such as obesity and insulin resistance) and improvements in vascular health through an improved redox and inflammatory status, but also reduced sympathetic overactivation and non-traditional mechanisms such as increased secretion of myokines.
Collapse
Affiliation(s)
| | - Pedro Carrera-Bastos
- Centre for Primary Health Care Research, Lund University/Region Skane, Skane University Hospital, Malmö, Sweden
| | - Beatriz G Gálvez
- Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain
| | - Gema Ruiz-Hurtado
- Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.,CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - José M Ordovas
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.,IMDEA Alimentacion, Madrid, Spain
| | - Luis M Ruilope
- Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.,CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Alejandro Lucia
- Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain. .,Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.
| |
Collapse
|
|
37
|
He FJ, Tan M, Ma Y, MacGregor GA. Salt Reduction to Prevent Hypertension and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol 2020; 75:632-647. [PMID: 32057379 DOI: 10.1016/j.jacc.2019.11.055] [Citation(s) in RCA: 323] [Impact Index Per Article: 64.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/04/2019] [Accepted: 11/19/2019] [Indexed: 12/21/2022]
Abstract
There is strong evidence for a causal relationship between salt intake and blood pressure. Randomized trials demonstrate that salt reduction lowers blood pressure in both individuals who are hypertensive and those who are normotensive, additively to antihypertensive treatments. Methodologically robust studies with accurate salt intake assessment have shown that a lower salt intake is associated with a reduced risk of cardiovascular disease, all-cause mortality, and other conditions, such as kidney disease, stomach cancer, and osteoporosis. Multiple complex and interconnected physiological mechanisms are implicated, including fluid homeostasis, hormonal and inflammatory mechanisms, as well as more novel pathways such as the immune response and the gut microbiome. High salt intake is a top dietary risk factor. Salt reduction programs are cost-effective and should be implemented or accelerated in all countries. This review provides an update on the evidence relating salt to health, with a particular focus on blood pressure and cardiovascular disease, as well as the potential mechanisms.
Collapse
Affiliation(s)
- Feng J He
- Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
| | - Monique Tan
- Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Yuan Ma
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Graham A MacGregor
- Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| |
Collapse
|
|
38
|
Agócs R, Sugár D, Szabó AJ. Is too much salt harmful? Yes. Pediatr Nephrol 2020; 35:1777-1785. [PMID: 31781959 PMCID: PMC7384997 DOI: 10.1007/s00467-019-04387-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 09/18/2019] [Accepted: 09/27/2019] [Indexed: 01/11/2023]
Abstract
The contribution of high sodium intake to hypertension and to the severity of immune-mediated diseases is still being heatedly debated in medical literature and in the lay media. This review aims to demonstrate two conflicting views on the topic, with the first part citing the detrimental effects of excessive salt consumption. Sodium plays a central role in volume and blood pressure homeostasis, and the positive correlation between sodium intake and blood pressure has been extensively researched. Despite the fact that the average of global daily salt consumption exceeds recommendations of international associations, health damage from excessive salt intake is still controversial. Individual differences in salt sensitivity are in great part attributed to this contradiction. Patients suffering from certain diseases as well as other vulnerable groups-either minors or individuals of full age-exhibit more pronounced blood pressure reduction when consuming a low-sodium diet. Furthermore, findings from the last two decades give insight into the concept of extrarenal sodium storage; however, the long-term consequences of this phenomenon are lesser known. Evidence of the relationship between sodium and autoimmune diseases are cited in the review, too. Nevertheless, further clinical trials are needed to clarify their interplay. In conclusion, for salt-sensitive risk groups in the population, even stricter limits of sodium consumption should be set than for young, healthy individuals. Therefore, the question raised in the title should be rephrased as follows: "how much salt is harmful" and "for whom is elevated salt intake harmful?"
Collapse
Affiliation(s)
- Róbert Agócs
- 1st Department of Paediatrics, Semmelweis University, Bókay János u. 53-54, Budapest, H-1083, Hungary
| | - Dániel Sugár
- 1st Department of Paediatrics, Semmelweis University, Bókay János u. 53-54, Budapest, H-1083, Hungary
| | - Attila J Szabó
- 1st Department of Paediatrics, Semmelweis University, Bókay János u. 53-54, Budapest, H-1083, Hungary.
- MTA-SE Paediatrics and Nephrology Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
| |
Collapse
|
|
39
|
Takeda R, Stickford AS, Best SA, Yoo JK, Fu Q. Salt intake impacts sympathetic neural control but not morning blood pressure surge in premenopausal women with a history of normal pregnancy. Am J Physiol Heart Circ Physiol 2020; 319:H571-H581. [PMID: 32734815 DOI: 10.1152/ajpheart.00197.2020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Salt intake may alter blood pressure (BP) regulation, but no study has investigated the impact of salt reduction versus salt loading on morning blood pressure surge (MBPS) and sympathetic neural control in premenopausal women with a history of normal pregnancy. Nine healthy women (42 ± 3 yr; mean ± SD) were given a low-salt diet (LS; 50 mEq sodium/day) and high-salt diet (HS; 250 mEq sodium/day) for 1 wk each (~2 mo apart with the order randomized), while water intake was ad libitum. Ambulatory BP at 24 h was measured, and the percent change in blood volume (BV) was calculated following LS and HS. MBPS was defined as the morning systolic BP (averaged for 2 h after wake-up) minus the lowest nocturnal systolic BP. Beat-by-beat BP, heart rate, and muscle sympathetic nerve activity (MSNA) were measured during supine rest. Signal averaging was used to characterize changes in beat-by-beat mean arterial pressure and total vascular conductance following spontaneous MSNA bursts to assess sympathetic vascular transduction. Ambulatory BP and MBPS (32 ± 7 vs. 26 ± 12 mmHg, P = 0.208) did not differ between LS and HS. From LS to HS, BV increased by 4.3 ± 3.7% (P = 0.008). MSNA (30 ± 20 vs. 18 ± 13 bursts/100 heartbeats, P = 0.005) was higher, whereas sympathetic vascular transduction was lower in LS than HS (both, P < 0.01). Changes in MSNA from LS to HS were correlated to percent changes in BV (r = -0.673; P = 0.047). Thus, salt intake affects sympathetic neural control but not MBPS in premenopausal women with a history of normal pregnancy. The underlying mechanisms remain unknown; however, alterations in sympathetic vascular transduction may, in part, contribute.NEW & NOTEWORTHY This is the first study to demonstrate that MBPS and ambulatory BP were not affected by salt intake despite a significant change in sympathetic outflow in healthy premenopausal women with a history of normal pregnancy. This may be due to compensatory adaptations in MSNA and sympathetic vascular transduction during salt reduction versus salt loading.
Collapse
Affiliation(s)
- Ryosuke Takeda
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas
| | - Abigail S Stickford
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas
| | - Stuart A Best
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jeung-Ki Yoo
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas
| | - Qi Fu
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,University of Texas Southwestern Medical Center, Dallas, Texas
| |
Collapse
|
|
40
|
Grotle AK, Macefield VG, Farquhar WB, O'Leary DS, Stone AJ. Recent advances in exercise pressor reflex function in health and disease. Auton Neurosci 2020; 228:102698. [PMID: 32861944 DOI: 10.1016/j.autneu.2020.102698] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/01/2020] [Accepted: 07/02/2020] [Indexed: 01/11/2023]
Abstract
Autonomic alterations at the onset of exercise are critical to redistribute cardiac output towards the contracting muscles while preventing a fall in arterial pressure due to excessive vasodilation within the contracting muscles. Neural mechanisms responsible for these adjustments include central command, the exercise pressor reflex, and arterial and cardiopulmonary baroreflexes. The exercise pressor reflex evokes reflex increases in sympathetic activity to the heart and systemic vessels and decreases in parasympathetic activity to the heart, which increases blood pressure (BP), heart rate, and total peripheral resistance through vasoconstriction of systemic vessels. In this review, we discuss recent advancements in our understanding of exercise pressor reflex function in health and disease. Specifically, we discuss emerging evidence suggesting that sympathetic vasoconstrictor drive to the contracting and non-contracting skeletal muscle is differentially controlled by central command and the metaboreflex in healthy conditions. Further, we discuss evidence from animal and human studies showing that cardiovascular diseases, including hypertension, diabetes, and heart failure, lead to an altered exercise pressor reflex function. We also provide an update on the mechanisms thought to underlie this altered exercise pressor reflex function in each of these diseases. Although these mechanisms are complex, multifactorial, and dependent on the etiology of the disease, there is a clear consensus that several mechanisms are involved. Ultimately, approaches targeting these mechanisms are clinically significant as they provide alternative therapeutic strategies to prevent adverse cardiovascular events while also reducing symptoms of exercise intolerance.
Collapse
Affiliation(s)
- Ann-Katrin Grotle
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, United States of America
| | | | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Donal S O'Leary
- Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Audrey J Stone
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, United States of America.
| |
Collapse
|
|
41
|
Smiljanec K, Mbakwe AU, Ramos-Gonzalez M, Pohlig RT, Lennon SL. Antioxidant cocktail following a high-sodium meal does not affect vascular function in young, healthy adult humans: a randomized controlled crossover trial. Nutr Res 2020; 79:13-22. [PMID: 32610254 DOI: 10.1016/j.nutres.2020.05.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/06/2020] [Accepted: 05/18/2020] [Indexed: 02/06/2023]
Abstract
Chronic high sodium intake is a risk factor for cardiovascular disease as it impairs vascular function through an increase in oxidative stress. The objective of this study was to investigate the acute effects of a high-sodium meal (HSM) and antioxidant (AO) cocktail on vascular function. We hypothesized that a HSM would impair endothelial function, and increase arterial stiffness and wave reflection, while ingestion of the AO cocktail would mitigate this response. Healthy adults ingested either an AO cocktail (vitamin C, E, alpha-lipoic acid) or placebo (PLA) followed by a HSM (1500 mg) in a randomized crossover blinded design. Blood pressure (BP), endothelial function (flow-mediated dilation; FMD) and measures of arterial stiffness (pulse wave velocity; PWV) and wave reflection (augmentation index; AIx) were made at baseline and 30, 60, 90, and 120 min after meal consumption. Forty-one participants (20M/21W; 24 ± 1 years; BMI 23.4 ± 0.4 kg/m2) completed the study. Mean BP increased at 120 min relative to 60 min (60 min: 79 ± 1; 120 min: 81 ± 1 mmHg; time effect P = .01) but was not different between treatments (treatment × time interaction P = .32). AIx decreased from baseline (time effect P < .001) but was not different between treatments (treatment × time interaction P = .31). PWV (treatment × time interaction, P = .91) and FMD (treatment × time interaction P = .65) were also not different between treatments. In conclusion, a HSM does not acutely impair vascular function suggesting young healthy adults can withstand the acute impact of sodium on the vasculature and therefore, the AO cocktail is not necessary to mitigate the response.
Collapse
Affiliation(s)
- Katarina Smiljanec
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
| | - Alexis U Mbakwe
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
| | | | - Ryan T Pohlig
- Biostatistics Core Facility, University of Delaware, STAR, Newark, DE.
| | - Shannon L Lennon
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
| |
Collapse
|
|
42
|
D'Elia L, La Fata E, Giaquinto A, Strazzullo P, Galletti F. Effect of dietary salt restriction on central blood pressure: A systematic review and meta-analysis of the intervention studies. J Clin Hypertens (Greenwich) 2020; 22:814-825. [PMID: 32271997 PMCID: PMC8029708 DOI: 10.1111/jch.13852] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 02/21/2020] [Accepted: 03/09/2020] [Indexed: 01/11/2023]
Abstract
Central blood pressure (cBP) is highly associated with cardiovascular risk. Although reduction of salt intake leads to lower peripheral blood pressure (BP), the studies on cBP provided inconsistent results. Therefore, we performed a systematic review and a meta-analysis of the available intervention trials of salt reduction on cBP values to reach definitive conclusions. A systematic search of the online databases available (up to December 2018) was conducted including the intervention trials that reported non-invasively assessed cBP changes after two different salt intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random-effect model. Sensitivity, heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Fourteen studies met the pre-defined inclusion criteria and provided 17 cohorts with 457 participants with 1-13 weeks of intervention time. In the pooled analysis, salt restriction was associated with a significant reduction in augmentation index (9.3%) as well as central systolic BP and central pulse pressure. There was a significant heterogeneity among studies (I2 = 70%), but no evidence of publication bias. Peripheral BP changes seemed to partially interfere on the relationship between salt restriction and cBP. The results of this meta-analysis indicate that dietary salt restriction reduces cBP. This effect seems to be, at least in part, independent of the changes in peripheral BP.
Collapse
Affiliation(s)
- Lanfranco D'Elia
- Department of Clinical Medicine and Surgery, ESH Excellence Center of Hypertension, Federico II, University of Naples Medical School, Naples, Italy
| | | | - Alfonso Giaquinto
- Department of Clinical Medicine and Surgery, ESH Excellence Center of Hypertension, Federico II, University of Naples Medical School, Naples, Italy
| | - Pasquale Strazzullo
- Department of Clinical Medicine and Surgery, ESH Excellence Center of Hypertension, Federico II, University of Naples Medical School, Naples, Italy
| | - Ferruccio Galletti
- Department of Clinical Medicine and Surgery, ESH Excellence Center of Hypertension, Federico II, University of Naples Medical School, Naples, Italy
| |
Collapse
|
|
43
|
Migdal KU, Babcock MC, Robinson AT, Watso JC, Wenner MM, Stocker SD, Farquhar WB. The Impact of High Dietary Sodium Consumption on Blood Pressure Variability in Healthy, Young Adults. Am J Hypertens 2020; 33:422-429. [PMID: 32006422 DOI: 10.1093/ajh/hpaa014] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/06/2020] [Accepted: 01/31/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND High sodium (Na+) intake augments blood pressure variability (BPV) in normotensive rodents, without changes in resting blood pressure (BP). Augmented BPV is associated with end-organ damage and cardiovascular morbidity. It is unknown if changes in dietary Na+ influence BPV in humans. We tested the hypothesis that high Na+ feeding would augment BPV in healthy adults. METHODS Twenty-one participants (10 F/11 M; 26 ± 5 years; BP: 113 ± 11/62 ± 7 mm Hg) underwent a randomized, controlled feeding study that consisted of 10 days of low (2.6 g/day), medium (6.0 g/day), and high (18.0 g/day) salt diets. On the ninth day of each diet, 24-h urine samples were collected and BPV was calculated from 24-h ambulatory BP monitoring. On the tenth day, in-laboratory beat-to-beat BPV was calculated during 10 min of rest. Serum electrolytes were assessed. We calculated average real variability (ARV) and standard deviation (SD) as metrics of BPV. As a secondary analysis, we calculated central BPV from the 24-h ambulatory BP monitoring. RESULTS 24-h urinary Na+ excretion (low = 41 ± 24, medium = 97 ± 43, high = 265 ± 92 mmol/24 h, P < 0.01) and serum Na+ (low = 140.0 ± 2.1, medium = 140.7 ± 2.7, high = 141.7 ± 2.5 mmol/l, P = 0.009) increased with greater salt intake. 24-h ambulatory ARV (systolic BP ARV: low = 9.5 ± 1.7, medium = 9.5 ± 1.2, high = 10.0 ± 1.9 mm Hg, P = 0.37) and beat-to-beat ARV (systolic BP ARV: low = 2.1 ± 0.6, medium = 2.0 ± 0.4, high = 2.2 ± 0.8 mm Hg, P = 0.46) were not different. 24-h ambulatory SD (systolic BP: P = 0.29) and beat-to-beat SD (systolic BP: P = 0.47) were not different. There was a trend for a main effect of the diet (P = 0.08) for 24-h ambulatory central systolic BPV. CONCLUSIONS Ten days of high sodium feeding does not augment peripheral BPV in healthy, adults. CLINICAL TRIALS REGISTRATION NCT02881515.
Collapse
Affiliation(s)
- Kamila U Migdal
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
| | - Matthew C Babcock
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
- Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Austin T Robinson
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
- School of Kinesiology, Neurovascular Physiology Laboratory, Auburn University, Auburn, Alabama, USA
| | - Joseph C Watso
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Megan M Wenner
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
| | - Sean D Stocker
- Department of Medicine, Division of Renal-Electrolyte, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - William B Farquhar
- Department of Kinesiology & Applied Physiology, University of Delaware, Newark, Delaware, USA
| |
Collapse
|
|
44
|
Smiljanec K, Mbakwe A, Ramos Gonzalez M, Farquhar WB, Lennon SL. Dietary Potassium Attenuates the Effects of Dietary Sodium on Vascular Function in Salt-Resistant Adults. Nutrients 2020; 12:nu12051206. [PMID: 32344796 PMCID: PMC7281996 DOI: 10.3390/nu12051206] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 04/17/2020] [Accepted: 04/23/2020] [Indexed: 12/11/2022] Open
Abstract
The influence of dietary sodium and potassium on blood pressure (BP) has been extensively studied, however their impact on endothelial function, particularly any interactive effects, has received less attention. The purpose of this study was to determine if dietary potassium can offset the deleterious effect of high dietary sodium on endothelial function independent of BP. Thirty-three adults with salt-resistant BP (16 M and 17 F; 27 ± 1 year) completed seven days each of the following diets in a random order: a moderate potassium/low sodium diet (65 mmol potassium/50 mmol sodium; MK/LS), a moderate potassium/high sodium diet (65mmol potassium/300 mmol sodium; MK/HS) and a high potassium/high sodium (120 mmol potassium/300 mmol sodium; HK/HS). On day seven of each diet, 24-h ambulatory BP and a urine collection were performed. Brachial artery flow-mediated dilation (FMD) was measured in response to reactive hyperemia. Between diets, 24-h BP was unchanged confirming salt resistance (p > 0.05). Sodium excretion increased on both HS diets compared to MK/LS (p < 0.05) and potassium excretion was increased on the HK diet compared to MK/LS and MK/HS (p < 0.05) confirming diet compliance. FMD was lower in MK/HS (5.4 ± 0.5%) compared to MK/LS (6.7 ± 0.5%; p < 0.05) and HK/HS (6.4 ± 0.5%), while there was no difference between the MK/LS and HK/HS diets (p > 0.05). These data suggest that dietary potassium provides vascular protection against the deleterious effects of high dietary sodium by restoring conduit artery function.
Collapse
|
|
45
|
Shenouda N, Ramick MG, Lennon SL, Farquhar WB, Edwards DG. High dietary sodium augments vascular tone and attenuates low-flow mediated constriction in salt-resistant adults. Eur J Appl Physiol 2020; 120:1383-1389. [PMID: 32306153 DOI: 10.1007/s00421-020-04370-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 04/05/2020] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Low-flow mediated constriction (L-FMC) has emerged as a valuable and complementary measure of flow-mediated dilation (FMD) for assessing endothelial function non-invasively. High dietary sodium has been shown to impair FMD independent of changes in blood pressure (BP), but its effects on L-FMC are unknown. PURPOSE To test the hypothesis that high dietary sodium would attenuate brachial artery L-FMC in salt-resistant adults. METHODS Fifteen healthy, normotensive adults (29 ± 6 years) participated in a controlled feeding study. Following a run-in diet, participants completed a 7-day low sodium (LS; 20 mmol sodium/day) and 7-day high sodium (HS; 300 mmol sodium/day) diet in randomized order. On the last day of each diet, 24 h urine was collected and assessments of 24 h ambulatory BP and L-FMC were performed. Salt-resistance was defined as a change in 24 h ambulatory mean arterial pressure (MAP) between the LS and HS diets of ≤ 5 mmHg. Resting vascular tone and L-FMC were calculated from ultrasound-derived arterial diameters. RESULTS High dietary sodium increased serum sodium and urinary sodium excretion (p < 0.001 for both), but 24 h MAP was unchanged (p = 0.16) by design. High dietary sodium augmented vascular tone (LS: 91 ± 23%, HS: 125 ± 56%, p = 0.01) and attenuated L-FMC (LS: - 0.58 ± 0.99%, HS: 0.17 ± 1.23%, p = 0.008). CONCLUSION These findings in salt-resistant adults provide additional evidence that dietary sodium has adverse vascular effects independent of changes in BP.
Collapse
Affiliation(s)
- Ninette Shenouda
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - Meghan G Ramick
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA.,Department of Kinesiology, West Chester University, West Chester, PA, USA
| | - Shannon L Lennon
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA
| | - David G Edwards
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA.
| |
Collapse
|
|
46
|
Babcock MC, Robinson AT, Watso JC, Migdal KU, Martens CR, Edwards DG, Pescatello LS, Farquhar WB. Salt Loading Blunts Central and Peripheral Postexercise Hypotension. Med Sci Sports Exerc 2020; 52:935-943. [PMID: 31609296 PMCID: PMC7144834 DOI: 10.1249/mss.0000000000002187] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION High salt intake is a widespread cardiovascular risk factor with systemic effects. These effects include an expansion of plasma volume, which may interfere with postexercise hypotension (PEH). However, the effects of high salt intake on central and peripheral indices of PEH remain unknown. We tested the hypothesis that high salt intake would attenuate central and peripheral PEH. METHODS Nineteen healthy adults (7 female/12 male; age, 25 ± 4 yr; body mass index, 23.3 ± 2.2 kg·m; V[Combining Dot Above]O2peak, 41.6 ± 8.7 mL·min·kg; systolic blood pressure (BP), 112 ± 9 mm Hg; diastolic BP, 65 ± 9 mm Hg) participated in this double-blind, randomized, placebo-controlled crossover study. Participants were asked to maintain a 2300 mg·d sodium diet for 10 d on two occasions separated by ≥2 wk. Total salt intake was manipulated via ingestion of capsules containing either table salt (3900 mg·d) or placebo (dextrose) during each diet. On the 10th day, participants completed 50 min of cycling at 60% V[Combining Dot Above]O2peak. A subset of participants (n = 8) completed 60 min of seated rest (sham trial). Beat-to-beat BP was measured in-laboratory for 60 min after exercise via finger photoplethysmography. Brachial and central BPs were measured for 24 h after exercise via ambulatory BP monitor. RESULTS Ten days of high salt intake increased urinary sodium excretion (134 ± 70 (dextrose) vs 284 ± 74 mmol per 24 h (salt), P < 0.001), expanded plasma volume (7.2% ± 10.8%), and abolished PEH during in-laboratory BP monitoring (main effect of diet, P < 0.001). Ambulatory systolic BPs were higher for 12 h after exercise during the salt and sham trials compared with the dextrose trial (average change, 3.6 ± 2.1 mm Hg (dextrose), 9.9 ± 1.4 mm Hg (salt), 9.8 ± 2.5 mm Hg (sham); P = 0.01). Ambulatory central systolic BP was also higher during the salt trial compared with dextrose trial. CONCLUSION High salt intake attenuates peripheral and central PEH, potentially reducing the beneficial cardiovascular effects of acute aerobic exercise.
Collapse
Affiliation(s)
- Matthew C. Babcock
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| | - Austin T. Robinson
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| | - Joseph C. Watso
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| | - Kamila U. Migdal
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| | | | - David G. Edwards
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| | | | - William B. Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE
| |
Collapse
|
|
47
|
Barić L, Drenjančević I, Mihalj M, Matić A, Stupin M, Kolar L, Mihaljević Z, Mrakovčić-Šutić I, Šerić V, Stupin A. Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals. J Clin Med 2020; 9:jcm9030843. [PMID: 32244956 PMCID: PMC7141509 DOI: 10.3390/jcm9030843] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/15/2020] [Accepted: 03/18/2020] [Indexed: 01/07/2023] Open
Abstract
This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes’ intracellular hydrogen peroxide (H2O2) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group. All these parameters remained unaffected by vitamins supplementation. Matrix metalloproteinase 9, antioxidant enzymes Cu/Zn SOD and glutathione peroxidase 1, and leukocytes’ intracellular superoxide production remained unchanged after the protocols in both HS and HS+C+E groups. Importantly, multiple regression analysis revealed that FRAP was the most powerful predictor of AChID, while PORH was strongly predicted by both FRAP and renin-angiotensin system activity. Hereby, we demonstrated that oxidative dis-balance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals which could be prevented by antioxidative vitamins consumption.
Collapse
Affiliation(s)
- Lidija Barić
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
| | - Ines Drenjančević
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
| | - Martina Mihalj
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
- Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Anita Matić
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
| | - Marko Stupin
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
- Department for Cardiovascular Disease, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia
| | - Luka Kolar
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
| | - Zrinka Mihaljević
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
| | - Ines Mrakovčić-Šutić
- Department of Physiology and Immunology, Medical Faculty University of Rijeka, Ul. Braće Branchetta 20/1, HR-51000 Rijeka, Croatia;
| | - Vatroslav Šerić
- Department of Clinical Laboratory Diagnostics, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia;
| | - Ana Stupin
- Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; (L.B.); (I.D.); (M.M.); (A.M.); (M.S.); (L.K.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
- Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 10E, HR-31000 Osijek, Croatia
- Correspondence: ; Tel.: +385-31-512-800
| |
Collapse
|
|
48
|
Hirahatake KM, Bruno RS, Bolling BW, Blesso C, Alexander LM, Adams SH. Dairy Foods and Dairy Fats: New Perspectives on Pathways Implicated in Cardiometabolic Health. Adv Nutr 2020; 11:266-279. [PMID: 31555799 PMCID: PMC7442361 DOI: 10.1093/advances/nmz105] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/19/2019] [Accepted: 09/03/2019] [Indexed: 12/13/2022] Open
Abstract
Low-fat and nonfat dairy products have been promoted as part of a healthy dietary pattern by both US dietary guidelines and professional organizations for several decades. The basis for this recommendation stems in part from the putative negative cardiometabolic effects associated with saturated fat consumption. However, as nutrition research has shifted from a single nutrient to a whole-food/dietary pattern approach, the role of dairy foods and dairy fat in the diet-disease relationship is being reexamined. Most observational and experimental evidence does not support a detrimental relationship between full-fat dairy intake and cardiometabolic health, including risks of cardiovascular disease and type 2 diabetes. Indeed, an expanded understanding of the dairy food matrix and the bioactive properties of dairy fats and other constituents suggests a neutral or potentially beneficial role in cardiometabolic health. To consider how consuming dairy foods, including full-fat dairy, is associated with cardiometabolic health, this review provides an innovative perspective on mechanisms that link dairy consumption to 3 main biological systems at the core of metabolic health, the gastrointestinal, hepatic, and vascular systems.
Collapse
Affiliation(s)
- Kristin M Hirahatake
- Department of Epidemiology, College of Health Sciences, University of California, Irvine, CA, USA
| | - Richard S Bruno
- Human Nutrition Program, Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA
| | - Bradley W Bolling
- Department of Food Science, University of Wisconsin-Madison, Madison, WI, USA
| | - Christopher Blesso
- Department of Nutritional Sciences, College of Agriculture, Health and Natural Resources, University of Connecticut, Storrs, CT, USA
| | - Lacy M Alexander
- Department of Kinesiology, College of Health and Human Development, The Pennsylvania State University, State College, PA, USA
| | - Sean H Adams
- Arkansas Children's Nutrition Center, Little Rock, AR, USA,Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA,Address correspondence to SHA (e-mail: )
| |
Collapse
|
|
49
|
Del Giorno R, Ceresa C, Gabutti S, Troiani C, Gabutti L. Arterial Stiffness and Central Hemodynamics are Associated with Low Diurnal Urinary Sodium Excretion. Diabetes Metab Syndr Obes 2020; 13:3289-3299. [PMID: 33061491 PMCID: PMC7520137 DOI: 10.2147/dmso.s266246] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 08/01/2020] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Excessive salt intake is an important determinant of cardiovascular (CV) health, impacting arterial stiffness and central blood pressure. However, sodium exhibits several patterns of excretion in urine during day- and night-time, which could differently affect CV risk. Here, we sought to explore the relationship between the day:night urinary sodium excretion ratio and arterial stiffness and central hemodynamics in the general population. METHODS Cross-sectional analysis in 1062 subjects. Arterial stiffness (pulse-wave velocity, PWV), central blood pressure (central systolic blood pressure, cSBP; central diastolic blood pressure, cDBP), and other hemodynamic parameters were noninvasively assessed. Day- and night-time urinary sodium were separately detected. Analyses were performed according to the day:night urinary sodium excretion ratio tertiles (T1-T3). RESULTS Low day-time excretors (T1) showed significantly higher values of arterial stiffness when compared with high day-time excretors (T3) (cf-PWV 7.6 ± 1.9 vs 6.9 ± 1.5 m/sec; p ≤ 0.001), and higher central BP parameters (cSBP: 111.6 ± 12.1 vs 109.0 ± 11.1 mmHg, p ≤ 0.001; cDBP, 76.9 ± 9.2 vs 75.1 ± 9.3 mmHg, p ≤ 0.001). In multivariate linear-regression models (β, CI), the day:night ratio of sodium excretion was significantly associated with arterial stiffness (cf-PWV -0.386, -0.559, -0.213, p ≤ 0.001) and with central hemodynamic parameters (cSBP -1.655, -2.800, -0.510; p ≤ 0.001; cDBP -1.319, -2.218, -0.420, p ≤ 0.001). Associations persisted after controlling for multiple confounding factors. In logistic-regression models, the risk of increased arterial stiffness was significantly reduced as the day:night ratio of urinary sodium excretion increased (OR 0.40, 95% CI 0.25-0.65, p ≤ 0.001). CONCLUSION The individual, intra-daily pattern of urinary sodium excretion, characterised by low daytime excretion, is associated with increased arterial stiffness and central blood pressure. Further studies are advocated to clarify the clinical utility of assessing the daily pattern of sodium excretion.
Collapse
Affiliation(s)
- Rosaria Del Giorno
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Institute of Biomedicine, University of Southern Switzerland, Lugano, Switzerland
- Correspondence: Rosaria Del Giorno; Luca Gabutti Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona 6500, Switzerland; Institute of Biomedicine, University of Southern Switzerland, Lugano, SwitzerlandTel +41 91 811 94 08; +41 91 811 84 64 Email
| | - Christos Ceresa
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Sofia Gabutti
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Chiara Troiani
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Luca Gabutti
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Institute of Biomedicine, University of Southern Switzerland, Lugano, Switzerland
| |
Collapse
|
|
50
|
Alba BK, Stanhewicz AE, Dey P, Bruno RS, Kenney WL, Alexander LM. Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide. J Nutr 2020; 150:55-63. [PMID: 31504721 PMCID: PMC8659358 DOI: 10.1093/jn/nxz205] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 06/13/2019] [Accepted: 07/26/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking. OBJECTIVES We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms. METHODS We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger). RESULTS Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01). CONCLUSIONS These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.
Collapse
Affiliation(s)
- Billie K Alba
- Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA
| | - Anna E Stanhewicz
- Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA
| | - Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - W Larry Kenney
- Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA
| | - Lacy M Alexander
- Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA
| |
Collapse
|