STIMULATION OF ALPHA(2) ADRENOCEPTORS DILATES THE RAT MIDDLE CEREBRAL-ARTERY

Background: Because alpha(2) adrenoceptor agonists are used as adjunct s to anesthetics, their effects on the cerebrovascular circulation are of prime importance. We studied changes in the diameter of rat middle cerebral arteries after stimulation of alpha(2) adrenoceptors with UK 14,304. Methods: Rat middle cerebral arteries were isolated, cannulate d at each end with a glass micropipette, and pressurized to 85 mmHg. T he middle cerebral arteries were immersed in a bath (37 degrees C) con taining physiologic saline solution, and luminally perfused with physi ologic saline solution (100 mu l/ min). Changes in vessel diameter wer e measured after magnification with a microscope. Results: Resting dia meter of the middle cerebral arteries was 239 +/- 13 mu m (n = 8) for the first study. A dose-dependent dilation was produced by addition of UK14,304 to the extraluminal bath; a 10-15% increase in diameter occu rred at a concentration of 10(-4) M. The dilations produced by UK14,30 4 were blocked with selective alpha(2)-antagonists, idazoxan and rauwo lscine, but not by the selective alpha(1)-antagonist, prazosin. The di lations could be blocked by removal of the endothelium, or the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (10(-5) M). The inhibitory effects of N-nitro-L-arginine methyl ester were reverse d with the addition of 10(-3) M L-arginine, but not 10(-3) M D-arginin e. Furthermore, the dilation produced by UK14,304 was completely aboli shed with pertussis toxin (100 ng/ml). Conclusions: It was concluded t hat the stimulation of alpha(2) adrenoceptors with UK14,304 produced a dilation in the rat middle cerebral artery that (1) was dependent on intact endothelium, (2) involved nitric oxide, and (3) acted via a per tussis toxin-sensitive G protein.