COMBINED EFFECT OF L-ARGININE AND SUPEROXIDE-DISMUTASE ON THE SPASTICBASILAR ARTERY AFTER SUBARACHNOID HEMORRHAGE IN DOGS

To investigate the function of nitric oxide (a major endothelium-deriv ed relaxing factor) in cerebral arteries after subarachnoid hemorrhage (SAH) in vivo, several nitric oxide-related substances were administe red to dogs that had undergone double SAH. These included L-arginine ( a substrate for the formation of nitric oxide), N-G-monomethyl-L-argin ine (L-NMMA, an analog of L-arginine that inhibits the formation of ni tric oxide from L-arginine), and superoxide dismutase (SOD, which prot ects nitric oxide from oxidation by superoxide anion), which were give n via intracisternal injection. The diameter of the basilar artery was assessed angiographically. In intact dogs, intracisternal bolus injec tions of L-arginine (1, 10, or 100 mu mol) produced a dose-dependent i ncrease in the internal diameter of the basilar artery; conversely, L- NMMA reduced the diameter of the basilar artery from baseline in a dos e-dependent manner. On Days 4 and 7, after two intracisternal injectio ns of autologous blood, L-arginine produced transient vasodilation of the spastic basilar artery, whereas L-NMMA produced no significant vas oconstriction. The vasodilator effect of L-arginine after SAH was stro nger on Day 4 than on Day 7, but less than in intact dogs. Intracister nal injection of SOD, which caused no effect per se, enhanced the dura tion of the vasodilator effect of L-arginine on the basilar artery on Day 4 and both the magnitude and duration of that effect on Day 7. Thu s, the basal release of nitric oxide was impaired after SAH, but the a bility to synthesize nitric oxide in the vascular wall was not abolish ed. The finding that the simultaneous injection of SOD enhanced and pr olonged the vasodilation induced by sufficient exogenous L-arginine su ggests that the inactivation of nitric oxide by superoxide anion contr ibutes to the development of vasospasm.