Morin induces endothelium-dependent relaxation by activating TRPV4 channels in rat mesenteric arteries

Abstract

Morin, a natural flavonol, has been reported to have beneficial pharmacological effects. Although its vascular protective effects have been studied, little is known about its effects on the mesenteric artery and the underlying mechanisms. Transient receptor potential vanilloid type 4 (TRPV4) channels are one of the most important Ca2+-permeable cation channels in vascular endothelial cells and play an important role in regulating rat mesenteric vascular tone. In the present study, the myogenic effects of morin were investigated using wire and pressure myography in the isolated mesenteric artery. Morin induced endothelium-dependent relaxation of isolated rat mesenteric arteries in a concentration-dependent manner. In addition, morin stimulated relaxation by activating TRPV4-mediated Ca2+ influx without affecting the nitric oxide (NO), hydrogen peroxide (H2O2), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) pathways. In primary cultured rat mesenteric artery endothelial cells and over-expressing TRPV4 HEK 293 cells, the TRPV4 inhibitor HC067047 significantly reduced the morin-induced increase in intracellular Ca2+ concentration. Furthermore, in rats with hypertension induced by NꞶ-nitro-L-arginine methyl ester (L-NAME), oral administration of morin (50 mg/kg/day) decreased systolic blood pressure. In L-NAME-induced hypertensive rats, morin significantly improved the relaxation response of the arteries to acetylcholine. Thus, we demonstrated that morin induces endothelium-dependent relaxation in the rat mesenteric artery by acting on TRPV4 channels to mediate Ca2+ influx and attenuate blood pressure in L-NAME-induced hypertension, thereby highlighting the potential of morin in the treatment of hypertension.