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

Abstract

We have recently proposed that an endogenous cannabinoid may be an endothelium-derived hyperpolarizing factor (EDHF), and we have now characterized the cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxations 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, LY320135: at 2 µM ED₅₀ for carbachol was 10.4±2.6 nmol and R _max was 66.9±6.2%, at 10 µM 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 µM), or a CB₂ selective antagonist, SR144528 (100 nM–1 µM). None of the antagonists influenced vasorelaxation to either the potassium channel activator levcromakalim or sodium nitroprusside. Coupled to our previous observation that the CB₁ receptor antagonist SR141716A opposes EDHF-mediated relaxation, the present observations point to the involvement of a cannabinoid receptor, which may be CB₁ or CB₁-like, in EDHF-mediated vasorelaxation.