PMID: 2495353Mar 1, 1989Paper

Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels

The Journal of Pharmacology and Experimental Therapeutics
I CaveroM Mestre

Abstract

Cromakalim (BRL 34915), a K+ channel activator, and diltiazem relaxed isolated rat aortic rings contracted with a low KCl concentration (25 mM). Gilbenclamide (0.1-3 microM) did not modify base-line resting tension or responses to KCl but prevented the vasorelaxant effects of cromakalim without affecting those of diltiazem or nitrendipine. Cromakalim, in contrast to the latter compounds, did not relax aortic rings contracted with 55 mM KCl. In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, a 20-min i.v. infusion of cromakalim (5.0 micrograms/kg/min) lowered mean carotid artery blood pressure. This effect reached maximum after administration and was accompanied by decreases in systemic (35%), hindquarter (45%), mesenteric (27%), and renal (19%) vascular resistances. The blood pressure effects of cromakalim were not modified by BW 755C (lipo and cyclooxygenase inhibitor), idazoxan, methylatropine, methysergide, promethazine, propranolol, SCH 23390 (DA-1 receptor antagonist), S-sulpiride, RP 59227 (antagonist of platelet activating factor receptors) or by bilateral vagotomy associated with ligation of carotid arteries. However, in rats pretreated with the hypoglycemic sulfonylureas ...Continue Reading

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