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Stroke, Vol 23, 1522-1525, Copyright © 1992 by American Heart Association

ARTICLES

Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits

GC Bauknight Jr, FM Faraci and DD Heistad
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1009.

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 NG-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 less than 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.

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