Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jan 6, 2017; 6(1): 29-40
Published online Jan 6, 2017. doi: 10.5527/wjn.v6.i1.29
Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet
Gabriel Cao, Silvana Lorena Della Penna, Nicolás Martín Kouyoumdzian, Marcelo Roberto Choi, Susana Gorzalczany, Belisario Enrique Fernández, Jorge Eduardo Toblli, María Inés Rosón
Gabriel Cao, Silvana Lorena Della Penna, Nicolás Martín Kouyoumdzian, Marcelo Roberto Choi, Belisario Enrique Fernández, Jorge Eduardo Toblli, María Inés Rosón, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1122AAJ, Argentina
Susana Gorzalczany, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Cátedra de Farmacología, Universidad de Buenos Aires, Buenos Aires C1122AAJ, Argentina
Author contributions: All the authors contributed to the manuscript.
Supported by A grant from the Universidad de Buenos Aires (UBACYT 20020130200105BA).
Institutional review board statement: The study was reviewed and approved by the Universidad de Buenos Aires (UBACYT 20020130200105BA) and the Institutional Committee for Care and Use of Laboratory Animals of the School of Pharmacy and Biochemistry of University of Buenos Aires.
Institutional animal care and use committee statement: All animal procedures and experimental protocols were approved by the Institutional Committee for Care and Use of Laboratory Animals of the School of Pharmacy and Biochemistry of University of Buenos Aires (Protocol Number: 2100-15; file 0035638/15). Animals were used following international guiding principles and local regulations regarding the care and use of laboratory animals for biomedical research as well as the “International Ethical Guiding Principles for Biomedical Research on Animals” established by the CIOMS (Council for International Organizations of Medical Sciences).
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marcelo Roberto Choi, MD, PhD, Professor of Human Anatomy and Histology, School of Pharmacy and Biochemistry, University of Buenos Aires, Marcelo T de Alvear 2270, 4º Piso, Buenos Aires C1122AAJ, Argentina. marcelinkchoi@yahoo.com.ar
Telephone: +54-911-52852751
Received: July 8, 2016
Peer-review started: July 12, 2016
First decision: August 11, 2016
Revised: September 26, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: January 6, 2017
Abstract
AIM

To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.

METHODS

Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin II (Ang II), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry.

RESULTS

The intake of high sodium produced a slight but significant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang II and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang II and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR.

CONCLUSION

These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang II. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.

Keywords: Kidney, Angiotensin II, Tempol, Angiotensin 1-7, High sodium diet

Core tip: This study explored the effect of tempol on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system in rats fed high salt for 3 wk. A high salt diet altered the balance between opposing components of renal renin-angiotensin system (RAS), favouring the angiotensin II arm. Tempol supplementation improves the balance between the natriuretic and antinatriuretic components of the renal RAS.