15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and lomerizine

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+.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Arteries; Benzopyrans; Calcium Channel Blockers; Cromakalim; Dogs; Female; Guanidines; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Pinacidil; Piperazines; Potassium Channels; Prostaglandin Endoperoxides, Synthetic; Pyrroles; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Verapamil