Anandamide inhibits endothelin-1 production by human cultured endothelial cells: A new vascular action of this endocannabinoid

Abstract

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 (≥5 μmol/l) significantly decreased endothelin-1 production in a dose-dependent manner, a response not affected by the specific CB 1 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 CB 1 receptors. Therefore, we hypothesize that AEA effects on endothelial cells may lead to vasodilatation through independent concerted mechanisms, involving a non-CB 1 receptor-dependent inhibition of endothelin-1 production and a CB 1-mediated increase of NO. Copyright © 2007 S. Karger AG.