Resveratrol Attenuates Vasocontractile Responses to Phenylephrine and Potassium Chloride via a Nitric Oxide Synthase– and Endothelium–Independent Mechanism

Abstract

This study examined the effect of acute pre‐incubation without or with resveratrol (RSV) at increasing in‐bath concentrations (0, 20, 50, or 100 µM) on the dose‐dependent vasocontractile response stimulated by either the α1‐adrenergic receptor agonist phenylephrine (PE; ‐9.0 to ‐5.0 LogM) or potassium chloride (KCl; 0 to 60 mM) in isometrically‐mounted common carotid artery rings isolated from 20‐30 week old Spontaneously Hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). In both SHR and WKY, the contractile dose‐response curve to PE was increasingly blunted by preincubation with 20, 50, and 100 µM RSV, as evidenced by a RSV concentration‐dependent rightward shift of EC50 and decrease in maximum amplitude and area under the curve (p<0.05). The contractile dose‐response curve to KCl was similarly affected by preincubation with increasing concentrations of RSV (p<0.05). Neither nitric oxide synthase (NOS) inhibition nor endothelium removal was found to affect the ability of 50 µM RSV to attenuate either PE‐ or KCl‐stimulated contraction in SHR or WKY. These data indicate that RSV can attenuate vasocontractile activity stimulated by either receptor‐mediated (PE) activation or voltage‐mediated (KCl) activation via a vascular wall cell‐signaling mechanism that is independent of NOS or the endothelium. This suggests that RSV may act to attenuate contraction in the vascular wall by directly affecting central pathways of contractile activation, such as vascular smooth muscle calcium handling and/or sensitivity.Funded by NSERC Canada