Resveratrol Supplants Captopril's Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis

Carolina B A Restini; Arthur F E Garcia; Henrique M Natalin; Mariane F A Carmo; Vinicius F Nowicki; Elen Rizzi; Leandra N Z Ramalho

Resveratrol Supplants Captopril's Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis

Yale J Biol Med. 2022 Mar 31;95(1):57-69. eCollection 2022 Mar.

Authors

Carolina B A Restini¹, Arthur F E Garcia², Henrique M Natalin², Mariane F A Carmo², Vinicius F Nowicki², Elen Rizzi², Leandra N Z Ramalho³

Affiliations

¹ Department of Pharmacology & Toxicology, College of Osteopathic Medicine, Michigan State University, Clinton Township, MI, USA.
² Department of Biotechnology, University of Ribeirao Preto, Ribeirão Preto-SP, Brazil.
³ Department of Pathology and Legal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP, Brazil.

PMID: 35370490
PMCID: PMC8961705

Abstract

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6^th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.

Keywords: Captopril; Cardiac Remodeling and Fibrosis; Oxidative Stress; Renin-Angiotensin System (RAS); Renovascular Hypertension; Resveratrol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Captopril / pharmacology
Humans
Hypertension*
Male
Rats
Rats, Wistar
Renal Artery Obstruction* / complications
Renal Artery Obstruction* / drug therapy
Resveratrol / pharmacology
Ventricular Remodeling / physiology

Substances

Captopril
Resveratrol