International Journal of Medical Sciences

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27 May 2019

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Int J Med Sci 2019; 16(5):644-653. doi:10.7150/ijms.31075

Research Paper

Naringenin Ameliorates Renovascular Hypertensive Renal Damage by Normalizing the Balance of Renin-Angiotensin System Components in Rats

Zhizhi Wang1, Shanshan Wang1, Jianqiao Zhao2, Changan Yu3, Yi Hu1, Yimin Tu2, Zufang Yang2, Jingang Zheng1,2,4, Yong Wang1,4✉, Yanxiang Gao4✉

1. Department of Cardiology, China-Japan Friendship School of Clinical Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100029, China;
2. Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China;
3. Central Laboratory of Cardiovascular Disease, China-Japan Friendship Hospital, Beijing 100029, China;
4. Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China.

Abstract

Background: Naringenin, a member of the dihydroflavone family, has been shown to have a protective function in multiple diseases. We previously demonstrated that naringenin played a protective role in hypertensive myocardial hypertrophy by decreasing angiotensin-converting enzyme (ACE) expression. The kidney is a primary target organ of hypertension. The present study tested the effect of naringenin on renovascular hypertensive kidney damage and explored the underlying mechanism.

Methods and Results: An animal model of renovascular hypertension was established by performing 2-kidney, 1-clip (2K1C) surgery in Sprague Dawley rats. Naringenin (200 mg/kg/day) or vehicle was administered for 10 weeks. Blood pressure and urinary protein were continuously monitored. Plasma parameters, renal pathology and gene expression of nonclipped kidneys were evaluated by enzyme-linked immunosorbent assay, histology, immunohistochemistry, real-time polymerase chain reaction, and Western blot at the end of the study. Rats that underwent 2K1C surgery exhibited marked elevations of blood pressure and plasma Ang II levels and renal damage, including mesangial expansion, interstitial fibrosis, and arteriolar thickening in the nonclipped kidneys. Naringenin significantly ameliorated hypertensive nephropathy and retarded the rise of Ang II levels in peripheral blood but had no effect on blood pressure. 2K1C rats exhibited increases in the ACE/ACE2 protein ratio and AT1R/AT2R protein ratio in the nonclipped kidney compared with sham rats, and these increases were significantly suppressed by naringenin treatment.

Conclusions: Naringenin attenuated renal damage in a rat model of renovascular hypertension by normalizing the imbalance of renin-angiotensin system activation. Our results suggest a potential treatment strategy for hypertensive nephropathy.

Keywords: naringenin, hypertensive nephropathy, renin-angiotensin system

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wang Z, Wang S, Zhao J, Yu C, Hu Y, Tu Y, Yang Z, Zheng J, Wang Y, Gao Y. Naringenin Ameliorates Renovascular Hypertensive Renal Damage by Normalizing the Balance of Renin-Angiotensin System Components in Rats. Int J Med Sci 2019; 16(5):644-653. doi:10.7150/ijms.31075. Available from http://www.medsci.org/v16p0644.htm