EVIDENCE THAT ANANDAMIDE AND EDHF ACT VIA DIFFERENT MECHANISMS IN RATISOLATED MESENTERIC-ARTERIES

The endogenous cannabinoid, anandamide, has been suggested as an endot helium-derived hyperpolarizing factor (EDHF). We found that anandamide -evoked relaxation in isolated segments of rat mesenteric artery was a ssociated with smooth muscle hyperpolarization. However, although anan damide-evoked relaxation was inhibited by either charybdotoxin (ChTX) or iberiotoxin, inhibition of the relaxation to EDHF required a combin ation of ChTX and apamin. The relaxations induced by either anandamide or EDHF were not inhibited by the cannabinoid receptor (CB1) antagoni st SRI41716A, or mimicked by selective CB1 agonists. Thus, anandamide appears to cause smooth muscle relaxation via a CB1 receptor-independe nt mechanism and cannabinoid receptor activation apparently does not c ontribute to EDHF-mediated relaxation in this resistance artery.