Resveratrol enhances the protective effect of captopril against cardiac hypertrophy in the renovascular hypertension

AFE GARCIA1, HM NATALIN1, CBA RESTINI1, LNZ RAMALHO2. 1University of Ribeirão Preto, Ribeirão Preto, Brazil, 2University of São Paulo, Ribeirão Preto, Brazil

Hypertensive patients with renovascular disease have evidently shown lipid peroxidation partly related to the activation of the Renin-Angiotensin System (RAS), which, among other effects, triggers cardiac and vascular remodeling (1). Experimentally, hypertension is extensively studied through animal models like 2-Kidneys-1Clip (2K-1C) renovascular hypertension (achieved by a partial stenosis through a silver clip placement in the left renal artery) (2). The sustained increase in blood pressure is mainly due to the increased plasma renin activity and increased angiotensin-II (AngII) (3). Overproduction of superoxide anion has been observed in some vessels and in cardiac tissue from 2K-1C hypertensive animals (4). We evaluate the effect of the antioxidant Resveratrol (RESV) in improving the cardiac benefits of an Angiotensin Converting Enzyme inhibitor, Captopril (CAPT), by analyzing the Ventricular Hypertrophy Index (VHI) and the Systolic Blood Pressure (SBP) from 2K-1C rats (ethical approval: 007/2010). Six weeks after surgery, male Wistar rats (200g before surgery), considered 2K-1C when SBP >160mmHg (measured by tail pletismography), and normotensive 2K rats (laparotomy without having renal artery clipped) were submitted to different treatments (by gavage) 3 times/week: RESV 20mg/kg, vehicle, CAPT 6 mg/kg, and the association CAPT+RESV. At the end of the 3th week, SBP and VHI were measured. The data were entered and analyzed in statistical software (Graph -pad - Prism4®), which is used Student 's t test for independent amostras and analysis of variance (ANOVA) one way, followed by the multiple comparison test Newman-Keuls. Values ​​are expressed as mean ± SEM (standard error of mean) and the differences established at p <0.05. VHI was significantly lower in 2K-1C treated with RESV+CAPT (2.62±0.07,n=8) when compared to 2K-1C untreated (3.41±0.07, n=9), and when compared to RESV treatment (3.11±0.14, n=14). 2K-1C rats treated with CAPT in association to RESV normalized VHI reaching the 2K untreated values (2.68±0.19, n=6). VHI in 2K-1C treated with RESV (3.11±0.14, n=14) was statistically reduced when compared to untreated 2K-1C (3.41±0.07, n=9). RESV+CAPT statistically reduced the SBP in 2K-1C (152.7±8.2 mmHg, n=9) when compared to untreated 2K-1C (183.22±6.22 mmHg, n=9). Although the RESV+CAPT treatment was effective in hypertensive rats, it did not normalize the SBP to the normotensive rats’ values (113.3±6.0 mmHg, n=6). CAPT and RESV had effectively reduced the VHI in 2K-1C rats, suggesting that treatments are acting in an additional way to attenuate the cardiac hypertrophy, whose development is related to the hypertensive status. In the 2K-1C, RESV and CAPT had the potential to reduce SBP.

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(2) Goldblatt H et al. (1934). The Journal of experimental medicine 59: 347-379.

(3) Guan S et al. (1992). Hypertension 20: 763-767.

(4) Oliveira JC et al. (2012) Open Journal of Medicinal Chemistry 2: 61-71