Inhibition of myogenic tone by mibefradil in rat cerebral arteries

Abstract The inhibitory effects of mibefradil (1.0 nM–1.0 μM), a putative selective inhibitor of T-type Ca 2+ channels that has peripheral and coronary vasodilating properties with few negative inotropic effects, on pressure-induced vasoconstrictions were compared to depolarization- and [Arg 8 ] vasopressin-induced tone in isolated middle cerebral arteries of the rat. The concentration–response relationships (IC 50 ) for myogenic tone (70±20 nM), depolarization- (53±9 nM) and vasopressin-induced tone (70±10 nM) were equally inhibited by mibefradil. Pressure-induced responses were consistently inhibited by mibefradil throughout the myogenically active pressure range (20–100 mm Hg). These results demonstrate that mibefradil is nonselective in inhibiting Ca 2+ dependent cerebral artery tone due to myogenic activation, depolarization or receptor activation.