VASODILATOR MECHANISMS OF ACTION OF AMRINONE DO NOT INVOLVE THE OPENING OF EITHER ATP-SENSITIVE OR CA2+-ACTIVATED K+ CHANNELS

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 (25 mM) 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.