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

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Abstract
Summary We have examined the effects of the potassium conductance enhancer cromakalim (BRL 34915) 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 (pK B 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 μmol/1) and nimodipine (0.001–1 μmol/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/1) 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 μmol/1). 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 μmol/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. Thus, although both cromakalim and nimodipine may have potential in the treatment of subarachnoidal haemorrhage and angina pectoris, differences in their therapeutic profiles are also likely to be found.