Mechanisms involved in oleamide-induced vasorelaxation in rat mesenteric resistance arteries. Eur J Pharmacol 2009 Apr 1;607(1-3):143-150
Date
04/21/2009Pubmed ID
19374826Abstract
Fatty acid amides are a new class of signaling lipids that have been implicated in diverse physiological and pathological conditions. Oleamide is a fatty acid amide that induces vasorelaxation. Here, we investigated the mechanisms behind the vasorelaxation effect of oleamide in rat mesenteric resistance arteries. Oleamide-induced concentration dependent (0.01 microM-10 microM) vasorelaxation in mesenteric resistance arteries. This relaxation was unaffected by the presence of the fatty acid amide hydrolase (FAAH) inhibitors. The cannabinoid type 1 (CB(1)) receptor antagonist, AM251 and the non-CB(1)/CB(2) cannabinoid receptor antagonist, O-1918, attenuated the oleamide vasodilatory response, however the cannabinoid CB(2) receptor antagonist, AM630, did not affect the vascular response. Moreover, inhibition of the transient receptor potential vanilloid (TRPV) 1 receptor with capsazepine shifted the oleamide-induced vasorelaxation response to the right. In agreement with the vascular functional data, the cannabinoid CB(1) and TRPV1 receptor proteins were expressed in mesenteric resistance arteries but cannabinoid CB(2) receptors and the FAAH enzyme were not. In endothelium-denuded arteries, the oleamide-mediated vasorelaxation was attenuated and cannabinoid CB(1) or non-CB(1)/CB(2) cannabinoid receptor blockade did not further reduce the dilatory response whereas TRPV1 antagonism further decreased the response. These findings indicate that cannabinoid receptors on the endothelium and endothelium-independent TRPV1 receptors contribute to the oleamide vasodilatory response. Taken together, these results demonstrate that the oleamide-induced vasorelaxation is mediated, in part, by cannabinoid CB(1) receptors, non-CB(1)/CB(2) cannabinoid receptors, and TRPV1 receptors in rat mesenteric resistance arteries. These mechanisms are overlapping in respect to oleamide-induced mesenteric resistance artery dilation.
