Anandamide and d9-thc dilation of cerebral arterioles is blocked by
indomethacin.
Ellis, Earl F., Sandra F. Moore, and Karen A. Willoughby.
Department of Pharmacology and Toxicology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
-0613
APStracts 2:0237H, 1995.
Anandamide (AN, arachidonyl ethanolamide) has previously been isolated
from brain and shown to be an endogenous ligand for the D9
-tetrahydrocannabinol (D9-THC) receptor. The purpose of these studies
was to determine whether AN or D9-THC can affect the cerebral
circulation. AN and D9-THC (10-13 - 10-3 M) were topically applied to
rabbit cerebral arterioles using the closed cranial window and
effects on diameter measured with a microscope. AN and D9-THC
similarly induced a dose-dependent dilation starting at
concentrations as low as 10-12 M. Maximum dilation for AN was 25% and
that for D9-THC 22%. Topical coapplication of indomethacin, a
cyclooxygenase inhibitor, completely blocked dilation, whereas the
free radical scavengers superoxide dismutase plus catalase or the
nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L
-NAME) had no effect on AN-induced dilation. The CSF level of PGE2
increased only in response to 10-7 M and greater AN and was not
affected by D9-THC. 3H-AN superfused through the cranial window was
20% converted to arachidonic acid. These results show that AN and D9
-THC can modulate cerebral arterioles, likely by stimulating release
and metabolism of endogenous arachidonic acid. Whether dilation is
due to vasodilator eicosanoids or other vasoactive agents whose
synthesis or release is cyclooxygenase-dependent is uncertain.
Received 28 November 1994; accepted in final form 31 May 1995.
APS Manuscript Number H1046-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.