Related Experiment Videos
An endogenous cannabinoid as an endothelium-derived vasorelaxant
M D Randall1, S P Alexander, T Bennett
1Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, United Kingdom.
Biochemical and Biophysical Research Communications
|December 4, 1996
Summary
Endothelium-derived hyperpolarizing factor (EDHF) may be an endogenous cannabinoid. Anandamide, a cannabinoid, causes vasodilation via hyperpolarization, suggesting it is the elusive EDHF.
Area of Science:
- Vascular Biology
- Endocrinology
- Pharmacology
Background:
- Nitric oxide (NO) is a key mediator of endothelium-dependent relaxation.
- An additional factor, endothelium-derived hyperpolarizing factor (EDHF), also contributes to vascular tone.
- The precise identity of EDHF has remained unknown, though it is suspected to be an arachidonic acid metabolite.
Purpose of the Study:
- To investigate the identity of EDHF.
- To determine if cannabinoid-like substances mediate EDHF-induced relaxations.
- To explore the role of anandamide as a potential EDHF.
Main Methods:
- Utilized rat mesenteric arterial beds to study relaxant responses.
- Employed the cannabinoid receptor antagonist SR141716A to block EDHF-mediated relaxations.
- Analyzed arachidonic acid metabolites using Thin-Layer Chromatography (TLC).
- Administered bradykinin in conscious rats to assess NO-independent vasodilator effects.
Main Results:
- EDHF-mediated relaxations in rat mesenteric arteries were inhibited by SR141716A.
- SR141716A also inhibited NO-independent depressor and vasodilator effects of bradykinin in conscious rats.
- A specific arachidonic acid metabolite, co-eluting with anandamide, accumulated during relaxations.
- Anandamide demonstrated potent vasorelaxant effects in the mesentery through a hyperpolarizing mechanism.
Conclusions:
- Endogenous cannabinoids, specifically anandamide, are implicated as endothelium-derived vasorelaxants.
- Anandamide acts via hyperpolarization, suggesting it may be the long-sought EDHF.
- These findings link cannabinoid signaling to EDHF activity in vascular regulation.