Regional Differences in the Actions of Verapamil and Isosorbide Dinitrate on Rabbit and Dog Vascular Smooth Muscle

The effects of verapamil and isosorbide dinitrate (ISDN) alone or together on mechanical responses of the rabbit coronary artery and mesenteric vein, and the dog coronary artery have been investigated. Verapamil, in concentrations exceeding 10 nM consistently inhibited and at 10 microM, blocked the contraction evoked by excess concentrations of K in these tissues, but agonist-induced contraction was not modified by the presence or absence of Ca. In concentrations greater than 1 microM, verapamil depolarized the membrane by inhibiting the K-conductance of the membrane. ISDN had little effect on the rabbit coronary artery in concentrations below 10 microM. In contrast, in the rabbit mesenteric vein and dog coronary artery, ISDN in concentrations over 1 microM inhibited the contraction evoked by excess concentrations of K or by agonists. Species differences were apparent in the actions of ISDN on vascular tissues. When verapamil and ISDN were simultaneously applied to the rabbit mesenteric vein and dog coronary artery, the K-induced contraction was markedly inhibited by an amount exceeding that produced by the sum of the contractions evoked by the individual application of both agents. An enhanced vasodilating action induced by simultaneous applications of both agents indicates a possible clinical benefit for anti-anginal treatment.