Reduced hemodynamic load aids low-dose resveratrol in reversing cardiovascular defects in hypertensive rats

Abstract

Cardiac hypertrophy and associated myocardial remodeling is one of the main complications of hypertension resulting in the development of heart failure. It is of great significance to explore novel treatments to reverse cardiac hypertrophy in hypertensives with or without affecting blood pressure. In the present study, we investigated whether low-dose resveratrol alone or in a combination with a blood pressure-lowering agent can reverse hypertension-induced cardiovascular dysfunction. Twenty-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were treated with resveratrol (2.5 mg kg⁻¹ per day) and/or hydralazine (25 mg kg⁻¹ per day) for 8 weeks. Blood pressure, cardiac structure and function, and electrocardiogram measurements were examined. Pressure myography of resistance arteries, histological examinations of heart tissues, oxidative stress and inflammatory measurements were also preformed to assess the efficacy of the treatment. Although resveratrol treatment alone was ineffective in reducing systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling, it significantly prevented the systolic impairment and reduced myocardial fibrosis, and reduced oxidative stress and inflammation in hypertensive rats. Furthermore, a combination of resveratrol with hydralazine treatment significantly reduced blood pressure, improved systolic and diastolic function, decreased fibrosis and improved vascular geometry. In summary, low-dose resveratrol itself was unable to reduce systolic blood pressure, diastolic blood pressure, diastolic dysfunction and vascular remodeling. However, resveratrol alone alleviated cardiac fibrosis and some of the functional abnormalities in SHRs. And a combination of resveratrol with hydralazine was more effective than resveratrol or hydralazine alone in improving overall cardiovascular parameters.

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…In general, lower doses of resveratrol (2.5 mg/kg/day) did not affect BP in several other studies performed in the same animal models [30][31][32]. Interestingly, while these findings suggest that the anti-hypertensive effects of resveratrol are dose-dependent, resveratrol (1 mg/kg/day) has been shown to reduce BP in DOCA-salt hypertensive rats [33], suggesting that under certain conditions, even low doses of resveratrol can lower BP and that the BP lowering effect of resveratrol is model-dependent.…”

“…In an effort to understand the potential of resveratrol to augment the effect of other antihypertensive medications, Thandapilly et al administered low dose resveratrol with and without hydralazine to SHR [31]. Although a low dose of resveratrol (2.5 mg/kg/day) alone did not affect the systolic or the diastolic pressure in the SHR [31,39], the combination of hydralazine and resveratrol treatment was significantly more effective than hydralazine alone in reducing both systolic and diastolic BP [31].…”

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

“…The process of cardiac remodeling has been found to be influenced by hemodynamic load 9 and neurohormonal activation; unfortunately, the exact mechanism has not been fully elucidated. Vascular endothelium directly contacts flowing blood and transduces hemodynamic stimuli into changes in endothelial structure and function.…”

Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

“…20 Resveratrol (2.5 mg/kg) was also shown to alleviate cardiac fibrosis and functional abnormalities in spontaneously hypertensive rats. 21 Similar antifibrotic effects of resveratrol have been observed in liver, 22,23 33 SPARC is a glycoprotein that has counter-adhesive properties. 34 It also takes part in proteolytic pathways by increasing the expression of collagenase and MMP-9, and activating MMP-2.…”