POTASSIUM CHANNEL OPENING PROPERTIES OF THIAZIDE DIURETICS IN ISOLATED GUINEA-PIG RESISTANCE ARTERIES

We examined the role of K+ channels in mediating the acute vascular actions of hydrochlorothiazide, indapamide, cicletanine, and cromakalim, studying the effect of K+ channel blockers on drug-induced relaxation and drug-induced Rb-86 efflux in guinea pig mesenteric arteries. Cromakalim-induced relaxation was unaffected by charybdotoxin, apamin, or phencyclidine (PCP) but was reduced by 75% (with 30 mu M cromakalim) by glibenclamide (p < 0.001). Cromakalim increased Rb-86 efflux from guinea pig vessels, an effect that was abolished by glibenclamide. Hydrochlorothiazide and cicletanine-induced relaxations have been shown to be inhibited by charybdotoxin by unaffected by glibenclamide, apamin, or PCP. Hydrochlorothiazide and cicletanine increased Rb-86 efflux from guinea pig mesenteric arteries. These increases were abolished by charybdotoxin. Indapamide-induced relaxation was not affected by incubation with any of the K+ channel blockers. Indapamide did not alter basal Rb-86 efflux. The results suggest that in guinea pig mesenteric arteries indapamide-induced relaxation is not mediated by an action on K+ channels. Cromakalim-induced effects are mediated by K-ATP. Large conductance K-Ca mediates the hydrochlorothiazide and cicletanine-induced vascular effects in part.