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

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1989 Sep 1

PMID 2812040

Citations 6

Authors

C R Cain

C D Nicholson

Affiliations

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Abstract

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)

Citing Articles

Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

Seager J, Murphy T, Garland C Br J Pharmacol. 1994; 111(2):525-32.

PMID: 8004397 PMC: 1909975. DOI: 10.1111/j.1476-5381.1994.tb14769.x.

Effects of pinacidil on cerebral and mesenteric arteries--influence of the endothelium.

Ryman T, Petersson J, Andersson K, Brandt L, Hogestatt E Naunyn Schmiedebergs Arch Pharmacol. 1993; 348(3):298-304.

PMID: 7901778 DOI: 10.1007/BF00169159.

5-hydroxytryptamine-stimulated accumulation of 1,2-diacylglycerol in the rabbit basilar artery: a role for protein kinase C in smooth muscle contraction.

Clark A, Garland C Br J Pharmacol. 1991; 102(2):415-21.

PMID: 2015423 PMC: 1918025. DOI: 10.1111/j.1476-5381.1991.tb12188.x.

A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells.

Volk K, Matsuda J, Shibata E J Physiol. 1991; 439:751-68.

PMID: 1910087 PMC: 1180133. DOI: 10.1113/jphysiol.1991.sp018691.

Comparison of cromakalim-induced relaxation of potassium precontracted rabbit, cat, and rat isolated cerebral arteries.

Parsons A, Ksoll E, Mackert J, Schilling L, Wahl M Naunyn Schmiedebergs Arch Pharmacol. 1991; 343(4):384-92.

PMID: 1906583 DOI: 10.1007/BF00179043.

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