Endothelium and cannabinoid receptor involvement in levcromakalim vasorelaxation

Levcromakalim was more potent at relaxing rat small mesenteric arteries with endothelium (EC50, 84+/-10 nM) than denuded vessels (EC50, 779+/-101 nM). The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride; 1 microM) shifted the levcromakalim concentration/response curve 7.6-fold rightwards in intact vessels but had no effect in de-endothelialised vessels. Similar effects occurred with pinacidil. Combination of the K+ channel blockers apamin (1 microM) and charybdotoxin (100 nM) shifted the levcromakalim concentration/response curve 3-fold rightwards only in intact vessels. It is concluded that levcromakalim and pinacidil relax mesenteric arteries partly by releasing a relaxing factor from endothelium, possibly an endogenous cannabinoid.