Stimulation of alpha(2) adrenoceptors dilates the rat middle cerebral artery

Background: Because alpha(2) adrenoceptor agonists are used as adjuncts 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 UK14,304. Methods: Rat middle cerebral arteries were isolated, cannulated at each end with a glass micropipette, and pressurized to 85 mmHg. The middle cerebral arteries were immersed in a bath (37 degrees C) containing physiologic saline solution, and luminally perfused with physiologic saline solution (100 mu l/ min). Changes in vessel diameter were measured after magnification with a microscope. Results: Resting diameter 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 occurred at a concentration of 10(-4) M. The dilations produced by UK14,304 were blocked with selective alpha(2)-antagonists, idazoxan and rauwolscine, but not by the selective alpha(1)-antagonist, prazosin. The dilations 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 reversed with the addition of 10(-3) M L-arginine, but not 10(-3) M D-arginine. Furthermore, the dilation produced by UK14,304 was completely abolished with pertussis toxin (100 ng/ml). Conclusions: It was concluded that 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 pertussis toxin-sensitive G protein.