Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits.
OBJECTIVE
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.
Bauknight
G C
GC
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1009.
Faraci
F M
FM
Heistad
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D001127:Arginine Vasopressin; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine