IngentaConnect An Endogenous Cannabinoid as an Endothelium-Derived Vasorelaxant

Authors: Randall M.D.¹; Alexander S.P.H.¹; Bennett T.¹; Boyd E.A.²; Fry J.R.¹; Gardiner S.M.¹; Kemp P.A.¹; Mcculloch A.I.¹; Kendall D.A.¹

Source: Biochemical and Biophysical Research Communications, Volume 229, Number 1, December 1996 , pp. 114-120(7)

Publisher: Academic Press

Abstract:

Since the identification of nitric oxide (NO) as an important mediator of endothelium-dependent relaxation, it has become clear that there is an additional endothelial relaxant factor, termed the endothelium-derived hyperpolarizing factor (EDHF). The identity of EDHF has remained elusive, but it is thought to be an arachidonic acid metabolite. We now report that EDHF-mediated relaxations in the rat mesenteric arterial bed are blocked by a highly selective cannabinoid receptor antagonist, SR141716A, consistent with EDHF being a cannabinoid-like substance. Furthermore, in conscious rats, the NO-independent depressor and regional vasodilator effects of bradykinin were inhibited by SR141716A. The relaxations in the isolated mesentery were accompanied by the accumulation of an arachidonic acid metabolite, which co-eluted on TLC separation with arachidonoylethanolamide (anandamide), an endogenous cannabinoid derived from arachidonate. We further report that anandamide is a potent vasorelaxant in the mesentery, acting via a hyperpolarizing mechanism. These findings suggest that an endogenous cannabinoid is an endothelium-derived vasorelaxant, which may be EDHF.

Language: English

Document Type: Research article

Affiliations: 1: Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom 2: Department of Pharmaceutical Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom

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