Mechanisms involved in oleamide-induced vasorelaxation in rat mesenteric resistance arteries

Sudhahar Varadarajan, Sean Shaw, John D. Imig

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 μM-10 μM) vasorelaxation in mesenteric resistance arteries. This relaxation was unaffected by the presence of the fatty acid amide hydrolase (FAAH) inhibitors. The cannabinoid type 1 (CB1) receptor antagonist, AM251 and the non-CB1/CB2 cannabinoid receptor antagonist, O-1918, attenuated the oleamide vasodilatory response, however the cannabinoid CB2 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 CB1 and TRPV1 receptor proteins were expressed in mesenteric resistance arteries but cannabinoid CB2 receptors and the FAAH enzyme were not. In endothelium-denuded arteries, the oleamide-mediated vasorelaxation was attenuated and cannabinoid CB1 or non-CB1/CB2 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 CB1 receptors, non-CB1/CB2 cannabinoid receptors, and TRPV1 receptors in rat mesenteric resistance arteries. These mechanisms are overlapping in respect to oleamide-induced mesenteric resistance artery dilation.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalEuropean Journal of Pharmacology
Volume607
Issue number1-3
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Fingerprint

Mesenteric Arteries
Vasodilation
Cannabinoids
Cannabinoid Receptor Antagonists
Cannabinoid Receptor CB2
Cannabinoid Receptors
Endothelium
Amides
Blood Vessels
Fatty Acids
oleylamide
Dilatation
Arteries
Lipids

Keywords

  • Cannabinoid receptor
  • Endothelium
  • Fatty acid amide
  • Mesenteric artery
  • Oleamide

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mechanisms involved in oleamide-induced vasorelaxation in rat mesenteric resistance arteries. / Varadarajan, Sudhahar; Shaw, Sean; Imig, John D.

In: European Journal of Pharmacology, Vol. 607, No. 1-3, 01.04.2009, p. 143-150.

Research output: Contribution to journalArticle

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