The Action of Diazoxide on Isolated Vascular Smooth Muscle Electrophysiology and Contraction

Abstract

Diazoxide inhibits spontaneous motility and contractile responses to noradrenaline, serotonin, or procaine in isolated rabbit anterior mesenteric vein (A.M.V.). Diazoxide fails to inhibit noradrenaline-induced contractions in ouabain-depolarized isolated A.M.V. Sucrose gap recordings show that spontaneous electrical activity in A.M.V., in guinea pig taenia coli, and in estrogen-dominated rabbit uterus is inhibited by diazoxide. The addition of extra calcium failed to overcome the inhibitory effect of diazoxide on smooth muscle contraction except when tissues were depolarized and calcium itself was the contractile agonist. It is suggested that diazoxide ordinarily inhibits contraction in vascular smooth muscle by acting on a membrane-potential-dependent component of excitation–contraction coupling. An additional mechanism of action of diazoxide, which is nonmembrane-potential-dependent, can be unmasked in depolarized A.M.V. where diazoxide can antagonize calcium-induced contractions.