ENDOTHELIUM-DERIVED RELAXING FACTOR MODULATES NORADRENERGIC CONSTRICTION OF CEREBRAL ARTERIOLES IN RABBITS

Background and Purpose: Cerebral arterioles are relatively unresponsive to norepinephrine. We tested the hypothesis that release of endothelium-derived relaxing factor is stimulated by norepinephrine and attenuates adrenergic constriction of pial arterioles. Methods: In seven anesthetized New Zealand White rabbits, diameter of pial arterioles was measured through a cranial window. Responses to topical application of norepinephrine and arginine vasopressin were examined before and during application of N(G)-nitro-L-arginine, which inhibits synthesis of endothelium-derived relaxing factor. Results: Norepinephrine (10(-6) M) had no effect (0+/-3%, mean+/-SE) on arteriolar diameter under basal conditions. Norepinephrine decreased arteriolar diameter by 15+/-4% during application of nitro-L-arginine (10(-4) M) (p<0.05 versus basal response). L-arginine inhibited the effect of nitro-L-arginine on responses of pial arterioles to norepinephrine. In contrast to norepinephrine, constrictor responses of pial arterioles to vasopressin were not potentiated by nitro-L-arginine. Conclusions: Norepinephrine, but not arginine vasopressin, releases endothelium-derived relaxing factor, which inhibits constrictor responses of cerebral arterioles in rabbits. This mechanism contributes to the finding that cerebral vessels in rabbits are relatively unresponsive to noradrenergic stimuli.