Differential vasorelaxant effects of K(+)-channel openers and Ca(2+)-channel blockers on canine isolated arteries.
The vasorelaxant effects of the K(+)-channel openers, pinacidil and cromakalim, were compared with those of the Ca(2+)-channel blockers, verapamil and KB-2796 (1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride), in canine isolated coronary, renal, basilar and mesenteric arteries precontracted with U46619, a thromboxane A2 mimetic. The relaxation induced by pinacidil and cromakalim was greater in coronary than in other arteries, the magnitude of relaxation being in the order of coronary > renal > basilar > mesenteric arteries. The relaxant responses to both drugs were inhibited by glibenclamide, a blocker of ATP-sensitive K+ channels. The relaxation induced by verapamil and KB-2796, in contrast, was greater in basilar than in other arteries, the magnitude of relaxation being in the order of basilar > coronary > renal and mesenteric arteries. In fura-2-loaded, U46619-stimulated arteries, pinacidil and cromakalim produced a greater reduction in intracellular Ca2+ concentration and muscle tension in coronary than in mesenteric arteries, while verapamil and KB-2796 reduced these values more potently in basilar than in mesenteric arteries. These results suggest that K(+)-channel openers exhibit a vasorelaxant selectivity for coronary arteries, whereas Ca(2+)-channel blockers exhibit such selectivity for cerebral arteries. The selective vasorelaxant action induced by these drugs appears to correspond, in part, to their effects on the concentration of intracellular Ca2+.
Iwamoto
T
T
Department of Pharmacology, Kanebo Ltd, Osaka, Japan.
Nishimura
N
N
Morita
T
T
Sukamoto
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020110:Pinacidil; D010879:Piperazines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D006146:Guanidines; D010879:Piperazines; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020110:Pinacidil; D014700:Verapamil; C052424:lomerizine