Characterization of cannabinoid receptors coupled to vasorelaxation by endothelium-derived hyperpolarizing factor

We have recently proposed that an endogenous cannabinoid may be an endothel ium-derived hyperpolarizing factor (EDHF), and we have now characterized th e cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxa tions to carbachol (ED50=3.26+/-0.57 nmol; the maximum relaxation, R-max=87 .0+/-2.5%) were opposed by the selective cannabinoid CB1 antagonist, LY3201 35: at 2 mu M ED50 for carbachol was 10.4+/-2.6 nmol and R-max was 66.9+/-6 .2%, at 10 mu M ED50 was 15.9+/-4.0 nmol and R-max was 34.0+/-4.3%. However , these responses were unaffected by another putative CB1 ligand, AM630 (10 mu M), or a CB2 selective antagonist, SR144528 (100 nM-1 mu M). None of th e antagonists influenced vasorelaxation to either the potassium channel act ivator levcromakalim or sodium nitroprusside. Coupled to our previous obser vation that the CB1 receptor antagonist SR141716A opposes EDHF-mediated rel axation, the present observations point to the involvement of a cannabinoid receptor, which may be CB1 or CB1-like, in EDHF-mediated vasorelaxation.