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Wang R, Wang M, Du D, Shan Z, Bi L, Chen QH. Brain-Targeted Reactive Oxygen Species in Hypertension: Unveiling Subcellular Dynamics, Immune Cross-Talk, and Novel Therapeutic Pathways. Antioxidants (Basel) 2025; 14:408. [PMID: 40298629 PMCID: PMC12024053 DOI: 10.3390/antiox14040408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/23/2025] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Hypertension (HTN) is a complex disease with significant global health implications, driven by neural and oxidative mechanisms. Reactive oxygen species (ROS), once considered mere metabolic byproducts, are now recognized as one of the key contributors to dysfunction of the autonomic nerve system, which involves the onset and progression of HTN. This review highlights the dynamic roles of ROS in neuronal signaling, subcellular compartmentalization, and brain-immune interactions, focusing on their impacts on synaptic remodeling, neuroinflammation, and epigenetic modifications within key autonomic regions such as the paraventricular nucleus and rostral ventrolateral medulla. We discuss novel ROS sources, including microglia-derived and endoplasmic reticulum stress-related ROS, and their contributions to HTN. Subcellular dynamics, such as ROS signaling at mitochondria-associated membranes and neuronal microdomains, are explored as activators of the sympathetic nerve system. Emerging evidence has linked ROS to epigenetic regulation, including histone modifications and non-coding RNA expression, with sex-specific differences offering insights for the development of personalized therapies. Innovative therapeutic strategies targeting ROS involve precision delivery systems, subcellular modulators, and circadian-optimized antioxidants. We propose several priorities for future research, including the real-time imaging of brain ROS, translating preclinical findings into clinical applications, and leveraging precision medicine to develop tailored interventions based on ROS activity and genetic predisposition. Through emphasizing the spatial and temporal complexity of ROS in HTN, this review identifies novel therapeutic opportunities and establishes a foundation for targeted treatments to address this health challenge.
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Affiliation(s)
- Renjun Wang
- Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China; (R.W.); (M.W.)
- Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI 49931-1200, USA;
| | - Min Wang
- Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China; (R.W.); (M.W.)
| | - Dongshu Du
- School of Life Sciences, Shanghai University, Shanghai 200444, China;
| | - Zhiying Shan
- Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI 49931-1200, USA;
| | - Lanrong Bi
- Department of Chemistry, Michigan Technological University, Houghton, MI 49931-1200, USA
| | - Qing-Hui Chen
- Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI 49931-1200, USA;
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Yang X, Jin J, Cheng M, Xu J, Bai Y. The role of sacubitril/valsartan in abnormal renal function patients combined with heart failure: a meta-analysis and systematic analysis. Ren Fail 2024; 46:2349135. [PMID: 38869007 PMCID: PMC11177705 DOI: 10.1080/0886022x.2024.2349135] [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: 12/05/2023] [Accepted: 04/02/2024] [Indexed: 06/14/2024] Open
Abstract
AIMS This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. METHODS The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. RESULTS A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure. CONCLUSIONS Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.
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Affiliation(s)
- Xinyue Yang
- Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jingjing Jin
- Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Meijuan Cheng
- Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jinsheng Xu
- Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yaling Bai
- Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Kim GH. Primary Role of the Kidney in Pathogenesis of Hypertension. Life (Basel) 2024; 14:119. [PMID: 38255734 PMCID: PMC10817438 DOI: 10.3390/life14010119] [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: 12/09/2023] [Revised: 01/03/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Previous transplantation studies and the concept of 'nephron underdosing' support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation.
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Affiliation(s)
- Gheun-Ho Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea
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Elevated Vascular Sympathetic Neurotransmission and Remodelling Is a Common Feature in a Rat Model of Foetal Programming of Hypertension and SHR. Biomedicines 2022; 10:biomedicines10081902. [PMID: 36009448 PMCID: PMC9405620 DOI: 10.3390/biomedicines10081902] [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: 07/01/2022] [Revised: 08/01/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022] Open
Abstract
Hypertension is of unknown aetiology, with sympathetic nervous system hyperactivation being one of the possible contributors. Hypertension may have a developmental origin, owing to the exposure to adverse factors during the intrauterine period. Our hypothesis is that sympathetic hyperinnervation may be implicated in hypertension of developmental origins, being this is a common feature with essential hypertension. Two-animal models were used: spontaneously hypertensive rats (SHR-model of essential hypertension) and offspring from dams exposed to undernutrition (MUN-model of developmental hypertension), with their respective controls. In adult males, we assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), sympathetic nerve function (3H-tritium release), sympathetic innervation (immunohistochemistry) and vascular remodelling (histology). MUN showed higher SBP/DBP, but not HR, while SHR exhibited higher SBP/DBP/HR. Regarding the mesenteric arteries, MUN and SHR showed reduced lumen, increased media and adventitial thickness and increased wall/lumen and connective tissue compared to respective controls. Regarding sympathetic nerve activation, MUN and SHR showed higher tritium release compared to controls. Total tritium tissue/tyrosine hydroxylase detection was higher in SHR and MUN adventitia arteries compared to respective controls. In conclusion, sympathetic hyperinnervation may be one of the contributors to vascular remodelling and hypertension in rats exposed to undernutrition during intrauterine life, which is a common feature with spontaneous hypertension.
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Bi Q, Wang C, Cheng G, Chen N, Wei B, Liu X, Li L, Lu C, He J, Weng Y, Yin C, Lin Y, Wan S, Zhao L, Xu J, Wang Y, Gu Y, Shen XZ, Shi P. Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension. Immunity 2022; 55:1466-1482.e9. [PMID: 35863346 DOI: 10.1016/j.immuni.2022.06.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 04/05/2022] [Accepted: 06/22/2022] [Indexed: 12/18/2022]
Abstract
Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.
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Affiliation(s)
- Qianqian Bi
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Chao Wang
- Center of Stem Cell and Regenerative Medicine and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Guo Cheng
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Ningting Chen
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Bo Wei
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Xiaoli Liu
- Department of Neurology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Li Li
- Department of Pharmacy, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China
| | - Cheng Lu
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Jian He
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Yuancheng Weng
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Chunyou Yin
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Yunfan Lin
- Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, Zhejiang 314400, China
| | - Shu Wan
- Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Li Zhao
- Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Jiaxi Xu
- Department of Physiology and Pathophysiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi 710061, China
| | - Yi Wang
- Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
| | - Yan Gu
- Center of Stem Cell and Regenerative Medicine and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, Zhejiang 310058, China.
| | - Xiao Z Shen
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
| | - Peng Shi
- Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
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Increased sympathetic tone and hypothalamic–pituitary–adrenal (HPA) axis activation impact in metabolic parameters from hypertensive rats. ENDOCRINE AND METABOLIC SCIENCE 2021. [DOI: 10.1016/j.endmts.2021.100112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Gao HL, Yu XJ, Zhang Y, Wang CL, Lei YM, Yu JY, Zong DM, Liu KL, Zhang DD, Li Y, Tian H, Zhang NP, Kang YM. Astaxanthin Ameliorates Blood Pressure in Salt-Induced Prehypertensive Rats Through ROS/MAPK/NF-κB Pathways in the Hypothalamic Paraventricular Nucleus. Cardiovasc Toxicol 2021; 21:1045-1057. [PMID: 34537923 DOI: 10.1007/s12012-021-09695-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 09/08/2021] [Indexed: 10/20/2022]
Abstract
Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus.To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1β (IL-1β), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN.
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Affiliation(s)
- Hong-Li Gao
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Xiao-Jing Yu
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Yan Zhang
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Chen-Long Wang
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Yi-Ming Lei
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Jia-Yue Yu
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Dong-Miao Zong
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Kai-Li Liu
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Dong-Dong Zhang
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Ying Li
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Hua Tian
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China
| | - Nian-Ping Zhang
- Department of Clinical Medicine, Medical School of Shanxi Datong University, Datong, China.
| | - Yu-Ming Kang
- Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China.
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Luo G, Zhu JJ, Yao M, Xie KY. Computed tomography-guided chemical renal sympathetic nerve modulation in the treatment of resistant hypertension: A case report. World J Clin Cases 2021; 9:9970-9976. [PMID: 34877338 PMCID: PMC8610920 DOI: 10.12998/wjcc.v9.i32.9970] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/26/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Resistant hypertension (RH) has always been a difficult problem in clinical diagnosis and treatment. At present, there is no recognized safe and effective minimally invasive treatment.
CASE SUMMARY An 80-year-old woman was admitted to hospital due to trigeminal neuralgia (TN). The patient had a history of RH for more than 10 years and her blood pressure (BP) was not well-controlled. Before the treatment for TN, we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital. One year after the operation, she stopped taking antihypertensive drugs, and her BP was satisfactorily controlled within 4 years after surgery.
CONCLUSION Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.
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Affiliation(s)
- Ge Luo
- Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Jian-Jun Zhu
- Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Ming Yao
- Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
| | - Ke-Yue Xie
- Department of Anesthesiology and Pain, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
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Recurrent Posterior Reversible Encephalopathy Syndrome in an Adolescent Boy with End-Stage Renal Disease. Case Rep Pediatr 2021; 2021:6675454. [PMID: 33643673 PMCID: PMC7902131 DOI: 10.1155/2021/6675454] [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: 12/08/2020] [Revised: 01/20/2021] [Accepted: 01/25/2021] [Indexed: 12/20/2022] Open
Abstract
Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome, is a neurological entity characterized by acute change in consciousness, visual impairment, headache, and seizures. It is associated with autoimmune disease, immunosuppressive agents, organ transplantation, acute glomerulonephritis, and sepsis. Typically, vasogenic edema is seen in the white matter of parieto-occipital lobes but can also involve atypical locations such as frontal lobes, thalamus, basal ganglia, and gray matter. While occurring extensively in adults, few cases, especially recurrent episodes, have been described in children. We report a case of recurrent PRES in a 17-year-old boy with end-stage renal disease on a peritoneal dialysis program who initially presented with hypertension and seizures. He emergently received intravenous antihypertensive medication with immediate and sustained improvement in his mental status. Information about recurrent PRES in children is limited because it is not commonly seen. We examine the clinical features of PRES and highlight important points for the diagnosis and management of this rare syndrome. This report demonstrates the importance of pediatricians to consider PRES in the differential diagnosis in children presenting with acute altered mental status. Blood pressure measurements, which are often overlooked in pediatric care, may assist in correctly diagnosing patients.
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Hu Z, Li B, Wang Z, Hu X, Zhang M, Chen R, Wu Q, Jia F. The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the expression of the TGFβ receptor ALK5 in aorta remodeling. Mol Med Rep 2020; 22:387-397. [PMID: 32319652 PMCID: PMC7248509 DOI: 10.3892/mmr.2020.11088] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 03/18/2020] [Indexed: 12/12/2022] Open
Abstract
The sympathetic system is involved in the arterial diseases, but its mechanism remains poorly understood. The present study aimed to explore the impact of the sympathetic neurotransmitter norepinephrine (NE) on transforming growth factor (TGF) β signaling and the role of NE in aortic remodeling. Guanethidine was used to induce a regional chemical sympathetic denervation (CSD) in angiotensin II (AngII) and β-aminopropionitrile (BAPN)-induced aortic aneurysm models. The diameter of the aorta was measured, and elastic fiber staining was performed. TGFβ type I receptor kinase (ALK5) expression in rat aortic NE-treated vascular smooth muscle cells (VSMCs) was detected by reverse transcription-quantitative PCR and western blotting. The effects of NE and ALK5 overexpression on migration, proliferation, apoptosis and TGFβ signaling were also evaluated. Furthermore, adrenergic receptor blockers were used to determine which receptor was involved in the modulation on TGFβ signaling by NE. The results of the present study demonstrated that CSD protected rats from AngII+BAPN-induced aortic remodeling and aneurysm formation. Compared with the control group, NE inhibited VSMC proliferation and migration, but promoted apoptosis by suppressing ALK5 expression, reversing the effects of TGFβ signaling through the suppression of the SMAD-dependent canonical pathway and promotion of the non-canonical pathway. These effects were prevented by ALK5 overexpression. The inhibition of α- or β-adrenergic receptors alleviated the NE-mediated suppression of ALK5 expression. In conclusion, regional CSD protected rats from aortic aneurysm. NE inhibited SMAD2/3-dependent TGFβ signaling by suppressing ALK5 expression, which may serve an important role in VSMC biological functions. Both α- and β-adrenergic receptors were involved in the regulation of ALK5 expression by NE. Abnormal sympathetic innervation of the aorta may be used as a therapeutic target in aortic diseases.
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Affiliation(s)
- Zhipeng Hu
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Bowen Li
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Zhiwei Wang
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Xiaoping Hu
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Min Zhang
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Ruoshi Chen
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Qi Wu
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Fangyuan Jia
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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Insights into sympathetic nervous system and GPCR interplay in fetal programming of hypertension: a bridge for new pharmacological strategies. Drug Discov Today 2020; 25:739-747. [PMID: 32032706 DOI: 10.1016/j.drudis.2020.01.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 01/07/2020] [Accepted: 01/29/2020] [Indexed: 12/18/2022]
Abstract
Cardiovascular diseases (CVDs) are the most common cause of death from noncommunicable diseases worldwide. In addition to the classical CVD risk factors related to lifestyle and/or genetic background, exposure to an adverse intrauterine environment compromises fetal development leading to low birth weight and increasing offspring susceptibility to develop CVDs later in life, particularly hypertension - a process known as fetal programming of hypertension (FPH). In FPH animal models, permanent alterations have been detected in gene expression, in the structure and function of heart and blood vessels, compromising cardiovascular physiology and favoring hypertension development. This review focuses on the role of the sympathetic nervous system and its interplay with G-protein-coupled receptors, emphasizing strategies that envisage the prevention and/or treatment of FPH through interventions in early life.
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12
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Renal sympathetic denervation for treatment of hypertension: where are we now in 2019? Curr Opin Nephrol Hypertens 2019; 28:498-506. [PMID: 31268917 DOI: 10.1097/mnh.0000000000000532] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW Although sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment resistant hypertension, and early clinical studies had produced encouraging results, the first sham-controlled study (SYMPLICITY HTN-3) failed to achieve its primary efficacy endpoint. Lessons learnt from this trial, and the knowledge derived from further animal and autopsy work, have been applied in three recently published sham-controlled trials. RECENT FINDINGS These trials - SPYRAL OFF-MED, RADIANCE SOLO and SPYRAL ON-MED - using newer technologies, demonstrate a 5-10 mmHg incremental reduction in ambulatory SBP from RDN against sham-control, in patients with mild-to-moderate hypertension taking 0-3 drugs. SUMMARY These results provide proof of principle of the blood pressure-lowering effect of renal denervation. We now require data on long-term safety and durability of the procedure. Research is needed to identify predictive markers of response as about one-third of individuals do not respond to renal denervation. Hard-outcome data would be welcome but might be difficult to acquire. Individuals with treatment resistance are obvious treatment candidates, but RDN may also potentially benefit those with medication nonadherence and/or intolerance and those unwilling to take pills.
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Wilson AL, Gandhi J, Suh Y, Joshi G, Smith NL, Khan SA. Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment. Curr Hypertens Rev 2019; 16:115-127. [PMID: 30827252 PMCID: PMC7527543 DOI: 10.2174/1573402115666190301154100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 02/21/2019] [Accepted: 02/21/2019] [Indexed: 12/30/2022]
Abstract
Background Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH. Objective We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN. Methods We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as “resistant hypertension” and
“renal denervation.” Conclusion A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.
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Affiliation(s)
- Anthony L Wilson
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, United States
| | - Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, United States
| | - Yiji Suh
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, United States
| | - Gunjan Joshi
- Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY 11968, United States
| | - Noel L Smith
- Foley Plaza Medical, New York, NY 10007, United States
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11794, United States
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14
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Sodium sensitivity of blood pressure in Chinese populations. J Hum Hypertens 2019; 34:94-107. [PMID: 30631129 DOI: 10.1038/s41371-018-0152-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 11/15/2018] [Accepted: 12/06/2018] [Indexed: 12/12/2022]
Abstract
Hypertension is an enormous public-health challenge in the world due to its high prevalence and consequent increased cardiovascular disease morbidity and mortality. Observational epidemiologic studies and clinical trials have demonstrated a causal relationship between sodium intake and elevated blood pressure (BP). However, BP changes in response to sodium intervention vary among individuals-a trait called sodium sensitivity. This paper aims to review the recent advances in sodium-sensitivity research in Chinese and other populations. Older age, female gender, and black race are associated with high sodium sensitivity. Both genetic and environmental factors influence BP sodium sensitivity. Physical activity and dietary potassium intake are associated with reduced sodium sensitivity while obesity, metabolic syndrome, and elevated BP are associated with increased sodium sensitivity. Familial studies have documented a moderate heritability of sodium sensitivity. Candidate gene association studies, genome-wide association studies, whole-exome, and whole-genome sequencing studies have been conducted to elucidate the genomic mechanisms of sodium sensitivity. The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, the largest family-based feeding study to date, was conducted among 1906 Han Chinese in rural northern China. This study showed that ~32.4% of Chinese adults were sodium sensitive. Additionally, several genetic variants were found to be associated with sodium sensitivity. Findings from the GenSalt Study and others indicate that sodium sensitivity is a reproducible trait and both lifestyle factors and genetic variants play a role in this complex trait. Discovering biomarkers and underlying mechanisms for sodium sensitivity will help to develop individualized intervention strategies for hypertension.
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15
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Li J, He Q, Li Q, Huang R, Wei X, Pan X, Wu W. Decreased expression of Na+-H+ exchanger isoforms 1 and 3 in denervated spontaneously hypertensive rat kidney. Clin Exp Hypertens 2018; 41:235-243. [PMID: 29787310 DOI: 10.1080/10641963.2018.1469639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Jianling Li
- Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qiaoling He
- Department of Pharmacology, Affiliated Hospital of Guangxi Medical University, The First people’s Hospital of Nanning, Nanning, China
| | - Qingjie Li
- Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Rongjie Huang
- Department of Pharmacology, Affiliated Hospital of Guangxi Medical University, The First people’s Hospital of Nanning, Nanning, China
| | - Xiaoyan Wei
- Department of Pharmacology, Affiliated Hospital of Guangxi Medical University, The First people’s Hospital of Nanning, Nanning, China
| | - Xiaofeng Pan
- Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Weifeng Wu
- Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Gallibois CM, Jawa NA, Noone DG. Hypertension in pediatric patients with chronic kidney disease: management challenges. Int J Nephrol Renovasc Dis 2017; 10:205-213. [PMID: 28794651 PMCID: PMC5538700 DOI: 10.2147/ijnrd.s100891] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.
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Affiliation(s)
- Claire M Gallibois
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
- Faculty of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Natasha A Jawa
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Damien G Noone
- Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
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Majeed F, Yar T, Alsunni A, Alhawaj AF, AlRahim A, Alzaki M. Synergistic effect of energy drinks and overweight/obesity on cardiac autonomic testing using the Valsalva maneuver in university students. Ann Saudi Med 2017; 37:181-188. [PMID: 28578355 PMCID: PMC6150576 DOI: 10.5144/0256-4947.2017.181] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Obesity and caffeine consumption may lead to autonomic disturbances that can result in a wide range of cardiovascular disorders. OBJECTIVES To determine autonomic disturbances produced by the synergistic effects of overweight or obesity (OW/OB) and energy drinks. DESIGN Cross-sectional, analytical. SETTING Physiology department at a university in Saudi Arabia. SUBJECTS AND METHODS University students, 18-22 years of age, of normal weight (NW) and OW/OB were recruited by convenience sampling. Autonomic testing by the Valsalva ratio (VR) along with systolic and diastolic blood pressure, pulse pressure, and mean arterial blood pressure were measured at baseline (0 minute) and 60 minutes after energy drink consumption. MAIN OUTCOME MEASURE(S) Autonomic disturbance, hemodynamic changes. RESULTS In 50 (27 males and 23 females) subjects, 21 NW and 29 OW/OB, a significant decrease in VR was observed in OW/OB subjects and in NW and OW/OB females at 60 minutes after energy drink consumption. Values of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure were also significantly higher in OW/OB and in females as compared to NW and males. BMI was negatively correlated with VR and diastolic blood pressure at 60 minutes. CONCLUSION Obesity and energy drinks alter autonomic functions. In some individuals, OW/OB may augment these effects. LIMITATIONS Due to time and resource restraints, only the acute effects of energy drinks were examined.
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Affiliation(s)
- Farrukh Majeed
- Dr. Farrukh Majeed, Department of Physiology,, College of Medicine,, University of Dammam,, Al-Rakha, Dammam 31451, Saudi Arabia, +966 13 333 5132, , ORCID: http://orcid.org/0000-0002-2987-601X
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Renal Denervation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016. [PMID: 27815927 DOI: 10.1007/5584_2016_148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register]
Abstract
Sympathetic nervous system over-activity is closely linked with elevation of systemic blood pressure. Both animal and human studies suggest renal sympathetic nerves play an important role in this respect. Historically, modulation of sympathetic activity has been used to treat hypertension. More recently, catheter based renal sympathetic denervation was introduced for the management of treatment resistant hypertension. Sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment of resistant hypertension. Encouraging results of early studies led to a widespread adoption of the procedure for management of this condition. Subsequently a sham controlled randomised controlled study failed to confirm the benefit of renal denervation leading to a halt in its use in most countries in the world. However, critical analysis of the sham-controlled study indicates a number of flaws. A number of lessons have been learnt from this and other studies which need to be applied in future trials to ascertain the actual role of renal denervation in the management of treatment resistant hypertension before further implementation. This chapter deals with all these issues in detail.
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