Nitric oxide-dependent vasodilation induced by minoxidil in isolated rat aorta

Abstract

We examined the effect of endothelium and lipid emulsion on vasodilation induced by minoxidil at a toxic dose and determined the underlying mechanism. The effects of endothelial denudation, N-W-nitro-L-arginine methyl ester (L-NAME), methylene blue, 1H-[1,24 ]oxadiazolo [4,3-a] quinoxalin- 1 -one (ODQ), and glibenclamide, alone or in combination, on minoxidil-induced vasodilation in endothelium-intact rat aorta were examined. Additionally, the effects of lipid emulsion on minoxidil-induced membrane hyperpolarization and minoxidil concentration were examined. The vasodilatory effects of minoxidil at the toxic dose were higher in endothelium-intact aorta than in endothelium-denuded aorta. L-NAME, methylene blue, ODQ, and glibenclamide attenuated minoxidil-induced vasodilation of endothelium-intact rat aorta. Combined treatment with L-NAME and glibenclamide almost eliminated minoxidil- induced vasodilation. lIowever, lipid emulsion pretreatment did not significantly alter minoxidil-induced vasodilation. Lipid emulsion did not significantly alter minoxidil-induced membrane hyperpolarization and minoxidil concentration. Overall, minoxidil-induced vasodilation is mediated by ATP-sensitive potassium channels and pathways involving nitric oxide and guanylate cyclase.