Vasodilator mechanisms of action of amrinone do not involve the opening of either ATP-sensitive or Ca(2+)-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+ (KATP) and large-conductance Ca(2+)-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 (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 KATP or KCa channels.
Orito
K
K
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Satoh
K
K
Taira
N
N
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018999:Charybdotoxin; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D012604:Scorpion Venoms; D018999:Charybdotoxin; D000255:Adenosine Triphosphate; C027917:tetramethylammonium; D000676:Amrinone; D005905:Glyburide; D002118:Calcium