Comparison of the effects of cromakalim, a potassium conductance enhancer, and nimodipine, a calcium antagonist, on 5-hydroxytryptamine responses in a variety of vascular smooth muscle preparations.
We have examined the effects of the potassium conductance enhancer cromakalim (BRL34915) and the calcium entry blocker nimodipine upon 5-hydroxytryptamine (5-HT) induced contractions in ring preparations from rabbit basilar and mesenteric arteries, and from pig coronary arteries. Cumulative concentration-response (CR) curves to 5-HT were biphasic in basilar and mesenteric arteries, and monophasic in coronary arteries. Coronary artery 5-HT CR curves and the first component of the mesenteric artery 5-HT CR curve were antagonized by ketanserin (pKB values 8.9 and 8.8, respectively), whereas basilar artery CR curves were not. Prazosin antagonized the second component of the mesenteric 5-HT CR curve, but not that of the basilar artery. Cromakalim (0.1-10 mumols/l) and nimodipine (0.001-1 mumol/l) both caused reductions in resting tension in basilar and coronary arteries denuded of their endothelia, but this effect was not seen with mesenteric arteries. Procaine (5 mmol/l) abolished this vasorelaxant effect of cromakalim in basilar artery. Both agents concentration-dependently depressed the 5-HT CR curve in coronary artery, the effect of cromakalim was antagonized by lidocaine (100 mumols/l). In basilar artery, only the first component was cromakalim sensitive unlike nimodipine which depressed both components of the CR curve. In mesenteric artery, 5-HT CR curves were depressed by cromakalim, but only slightly affected by nimodipine (1 mumol/l). It is concluded that cromakalim, like nimodipine, possesses anti-vasospastic activity; however, differences exist in the sensitivity of the 5-HT mediated contractions of the three arterial preparations to the agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Cain
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Beecham-Wulfing Research Laboratories, Gronau (Leine), Federal Republic of Germany.
Nicholson
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D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013552:Swine
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D012702:Serotonin Antagonists; D019806:Cromakalim; D009553:Nimodipine; D007650:Ketanserin; D011224:Prazosin