Md. Randall et al., AN ENDOGENOUS CANNABINOID AS AN ENDOTHELIUM-DERIVED VASORELAXANT, Biochemical and biophysical research communications, 229(1), 1996, pp. 114-120
Since the identification of nitric oxide (NO) as an important mediator
of endothelium-dependent relaxation, it has become clear that there i
s an additional endothelial relaxant factor, termed the endothelium-de
rived hyperpolarizing factor (EDHF). The identity of EDHF has remained
elusive, but it is thought to be an arachidonic acid metabolite. We n
ow report that EDHF-mediated relaxations in the rat mesenteric arteria
l bed are blocked by a highly selective cannabinoid receptor antagonis
t, SR141716A, consistent with EDHF being a cannabinoid-like substance.
Furthermore, in conscious rats,.the NO-independent depressor and regi
onal vasodilator effects of bradykinin were inhibited by SR141716A. Th
e relaxations in the isolated mesentery were accompanied by the accumu
lation of an arachidonic acid metabolite, which co-eluted on TLC separ
ation with arachidonoylethanolamide (anandamide), an endogenous cannab
inoid derived from arachidonate. We further report that anandamide is
a potent vasorelaxant in the mesentery, acting via a hyperpolarizing m
echanism. These findings suggest that an endogenous cannabinoid is an
endothelium-derived vasorelaxant, which may be EDHF. (C) 1996 Academic
Press, Inc.