An endogenous cannabinoid as an endothelium-derived vasorelaxant

Biochem Biophys Res Commun. 1996 Dec 4;229(1):114-20. doi: 10.1006/bbrc.1996.1766.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Arachidonic Acids / metabolism*
  • Biological Factors / metabolism*
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / metabolism*
  • Endocannabinoids
  • Endothelium, Vascular / metabolism*
  • Humans
  • Male
  • Mesenteric Artery, Superior
  • Perfusion
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant
  • Splanchnic Circulation
  • Vasodilator Agents / metabolism*


  • Arachidonic Acids
  • Biological Factors
  • Cannabinoids
  • Endocannabinoids
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Vasodilator Agents
  • endothelium-dependent hyperpolarization factor
  • Arachidonic Acid
  • Rimonabant
  • anandamide