endothelin-1 and 9-(2-hydroxy-3-nonyl)adenine

The endogenous cannabinoid receptor agonist anandamide (AEA) exerts vascular effects such as vasodilatation and hypotension. In this study, we determined the effect of AEA on endothelin-1 production by cultured human umbilical vein endothelial cells. Anandamide (>or=5 micromol/l) significantly decreased endothelin-1 production in a dose-dependent manner, a response not affected by the specific CB1 receptor antagonist/inverse agonist SR-141716A. Adenosine, via activation of adenosine receptors (also targets for SR-141716A), was not involved in these effects. Conversely, AEA increased nitric oxide (NO) production, an effect inhibited by SR-141716A, indicating the involvement of CB1 receptors. Therefore, we hypothesize that AEA effects on endothelial cells may lead to vasodilatation through independent concerted mechanisms, involving a non-CB1 receptor-dependent inhibition of endothelin-1 production and a CB1-mediated increase of NO.

Topics: Adenine; Adenosine; Arachidonic Acids; Cannabinoid Receptor Modulators; Cells, Cultured; Dose-Response Relationship, Drug; Endocannabinoids; Endothelial Cells; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Humans; Nitric Oxide; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Xanthines