Endothelium-Dependant Vasomotor Function in Spontaneously Hypertensive Rats Following Chronic Dietary Treatment with Resveratrol

Abstract

Essential hypertension is a disease involving impaired endothelium-dependant vasomotor function which is partially mediated through an increase in reactive oxygen species. Recent evidence has demonstrated that resveratrol (RSV), a polyphenol with antioxidant capabilities, alleviates this impaired endothelium-dependant vasomotor function and can provide cardiovascular health benefits. The aim of this study was to examine the effects of chronic resveratrol treatment for 28 days on the endothelium-dependant vasomotor function and hemodynamic measures of the common carotid artery (CCA) of Spontaneously Hypertensive rat (SHR) aged 20-22 weeks at a high (2.7 mg per day, equivalent to a 500mg dose in humans) and a low (0.027mg per day, equivalent to moderate red wine consumption in humans) dose. The 20-22 week old SHR (n=9) demonstrated an elevated mean arterial blood pressure compared to the normotensive control, Wistar Kyoto rats (WKY) (n=9) (p<0.001). The SHR also demonstrated decreased endothelium-dependant vasorelaxation and increased endothelium-dependant contraction, indicating impaired endothelium-dependant vasomotor function. Following chronic treatment with resveratrol for 28 days at a high dose maximal relaxation to acetylcholine (ACh) of phenylephrine (PE) pre-contracted CCA vessels was increased when compared to SHR CON (High 100.4 + 5.2%, CON 53.6 + 6%) (p<0.001). This difference is possibly mediated by improved nitric oxide (NO) bioavailability. This study also confirmed that SHR demonstrate increased endothelium-dependant contractions in quiescent, non pre-contracted rings of the CCA (P<0.001). High dose resveratrol treatment reduced SHR endothelium-dependant contraction in the CCA compared to SHR CON (High 55 + 5.4%, CON 68 + 5%) (p<0.05). This effect was likely mediated by an observed reduction in prostacyclin (PGI2) production, when compared to the SHR CON (p<0.05). This result is likely to be cause by inhibition of cycloxygenase 1 (COX 1) since reversal of SHR endothelium-dependant contraction is demonstrated following inhibition of COX 1, an interpretation supported by the observation that resveratrol treatment had no effect on the sensitivity of the thromboxane-prostaglandin receptor, and no effect on the protein expression of COX 1. This study indicates that chronic treatment with resveratrol at a high dose improves CCA endothelium- dependent vasomotor function in SHR via improved NO bioavailability and a reduction in endothelium-dependant PGI2-mediated contraction. These improvements in vasomotor function produced an alteration in vascular tone to a less contracted state. If these observations extend to the resistance vasculature they could contribute to the explanation for resveratrol-dependant reduction in mean arterial blood pressure.