2-Arachidonoylglycerol and Anandamide Oppositely Modulate Norepinephrine Release from the Rat Heart Sympathetic Nerves

Abstract

Anandamide (10^–7 and 10^–6 M) as well as a synthetic cannabinoid HU210 (10^–8 to 10^–6 M) suppressed the norepinephrine release evoked by perivascular nerve stimulation (PNS) of the rat heart Langendorff’s preparation. The effects of HU210 and the lower dose of anandamide were completely blocked by the cannabinoid CB₁-receptor antagonist AM251, while that of anandamide at 10^–6 M was partly mediated by arachidonate-derived metabolites. 2-Arachidonoylglycerol (2-AG), at 10^–6 M in the presence of DFP and indomethacin, increased PNS-evoked norepinephrine release, which was completely blocked by AM251. The present results suggest that the two endocannabinoids may oppositely participate in the CB₁-receptor-mediated modulation of sympathetic norepinephrine release.