The vasodilator effect of amrinone does not depend on the opening of ATP-sensitive or Ca2+-activated K+ channels.
Amrinone vasodilation appears K+-independent in this animal model; leaves open alternative mechanisms and human translation.
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+ (KATP) and large-conductance Ca2+-activated K+ (KCa) channels in the vasodilator effect of amrinone, we investigated whether amrinone-induced vasodilation would be antagonized by glibenclamide, a blocker of KATP channels, or by charybdotoxin or tetraethylammonium, blockers of KCa 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 KATP or KCa channels.
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Orito et al. (1994) studied this question.
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