Vasodilator Mechanisms of Action of Amrinone Do Not Involve the Opening of Either ATP-Sensitive or Ca²⁺-Activated K⁺ Channels

Abstract

ORITO, K., SATOH, K. and TAIRA, N. Vasodilator Mechanisms of Action of Amrinone Do Not Involve the Opening of Either ATP-sensitive or Ca²⁺--Activated K⁺ Channels. Tohoku J. Exp. Med., 1994, 172 (2), 163-173-Amrinone is more coronary vasodilatory than positive inotropic compared with other newer phosphodiesterase inhibitors. In order to explore possible involvements of ATP-sensitive K⁺ (K_ATP) and large-conductance Ca²⁺-activated K⁺ (K_Ca) channels in the vasodilator effect of amrinone, we investigated whether amrinone-induced vasodilation would be antagonized by glibenclamide, a blocker of K_ATP channels, or by charybdotoxin or tetraethylammonium, blockers of K_Ca channels. In isolated, blood-perfused canine papillary muscle preparations, the amrinone-induced increase in blood flow was not affected by glibenclamide given to support dogs. In canine large coronary arteries contracted with high (25mM) KCl, amrinone-induced relaxation was not affected by glibenclamide, charybdotoxin and tetraethylammonium. These results suggest that the vasodilator mechanisms of amrinone do not involve the opening of either K_ATP or K_Ca channels.