Resveratrol Attenuates Thromboxane‐Prostanoid Receptor‐Mediated Vasocontraction via NO‐ and Endothelium‐ Independent Mechanisms

Abstract

The purpose of this study was to investigate the effect of resveratrol (RSV) on thromboxane‐prostanoid receptor (TPr)‐mediated vasocontraction. Dose‐response to the TPr agonist U46619 (‐9.0 ‐ ‐6.0 LogM) was examined in vitro in tissue baths using isometrically mounted common carotid arterial rings isolated from 20‐30 week old Wistar Kyoto rats (WKY; n=8) and Spontaneously Hypertensive rats (SHR; n=8). Endothelium‐intact (E+) rings were pre‐incubated (for 30 minutes) with either no drug (ND); the nitric oxide synthase inhibitor L‐NAME (LN; 100 µM); RSV at either 20, 50, or 100 µM; or, LN+RSV‐20µM. Endothelium‐denuded (E‐) rings were pre‐incubated with either ND or RSV‐20µM. The EC50 for U46619 in E+ was decreased in LN vs. ND WKY (LN: ‐8.12±0.05 Log M vs ND: ‐7.72±0.06, p<0.05), but not SHR. The combination effect of E+ LN+RSV‐20 µM significantly decreased the maximum amplitude in WKY but not SHR. Increasing doses of RSV at 50 µM and 100 µM resulted in further increases in EC50 for both WKY (‐7.16±0.04 and ‐6.83±0.08, respectively) and SHR (‐7.17±0.06 and ‐6.80±0.04,respectively), while only WKY exhibited a significant (p<0.05) decrease in the maximum amplitude. In E‐, WKY (RSV‐20µM: ‐7.46±0.08 LogM vs. ND) and SHR (RSV‐20µM: ‐7.63±0.06 LogM vs. ND) had significantly increased EC50 with RSV‐20 µM incubation (p<0.05), while the maximum amplitude remained unaffected. These results suggest that acute pre‐incubation with RSV dose‐dependently attenuates TPr‐stimulated vasocontractile activity by a cell‐signalling mechanism that does not appear to require nitric oxide synthase or the endothelium.Funded by NSERC Canada