ANANDAMIDE AND DELTA(9)-THC DILATION OF CEREBRAL ARTERIOLES IS BLOCKED BY INDOMETHACIN

Anandamide (AN, arachidonyl ethanolamide) has been isolated from the b rain and shown to be an endogenous ligand for the Delta(9)-tetrahydroc annabinol (Delta(9)-THC) receptor. The purpose of these studies was to determine whether AN or Delta(9)-THC can affect the cerebral circulat ion. With the use of the closed cranial window AN and Delta(9)-THC (10 (-13)-10(-3) M) were topically applied to rabbit cerebral arterioles a nd effects on diameter were measured with a microscope. AN and Delta(9 )-THC similarly induced a dose-dependent dilation starting at concentr ations as low as 10(-12) M. Maximum dilation for AN was 25% and that f or Delta(9)-THC 22%. Topical coapplication of indomethacin, a cyclooxy genase inhibitor, completely blocked dilation, whereas the free radica l scavengers superoxide dismutase and catalase or the nitric oxide syn thase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) had no effe ct on AN-induced dilation. The cerebrospinal fluid level of prostaglan din E(2) increased only in response to 10(-7) M and greater AN and was not affected by Delta(9)-THC. [H-3]AN superfused through the cranial window was 20% converted to arachidonic acid. These results show that AN and Delta(9)-THC can modulate cerebral arterioles, likely by stimul ating release and metabolism of endogenous arachidonic acid. Whether d ilation is due to vasodilator eicosanoids, or other vasoactive agents whose synthesis or release is cyclooxygenase dependent, is uncertain.