Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain.
Neurons release nitric oxide (NO) in response to activation of receptors for the excitatory amino acid N-methyl-D-aspartate (NMDA). We examined the hypothesis that activation of receptors for NMDA produces dilatation of the cerebral microcirculation that is mediated by NO. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Under control conditions, topical NMDA produced concentration-related dilatation of pial arterioles. Dilatation in response to NMDA was inhibited selectively by MK-801 (an NMDA receptor antagonist) and tetrodotoxin, suggesting that responses to NMDA were receptor mediated and dependent on neuronal activation. Increases in arteriolar diameter in response to NMDA were not affected by L-arginine but were inhibited by NG-nitro-L-arginine, suggesting that the vasodilatation was mediated by NO. Dilatation of cerebral arterioles in response to NMDA was not inhibited by indomethacin, suggesting that cyclooxygenase products do not mediate the response. Using isolated cerebral arteries, we also examined whether NMDA elicited direct cerebral vascular effects. In intact arteries studied in vitro, NMDA had no effect on vascular tone, suggesting that cerebral arteries lack receptors for NMDA. These findings suggest that NO generated in response to activation of receptors for NMDA in vivo is neuronally derived and not due to a direct vascular effect. Thus, NO may mediate increases in local blood flow during increases in neuronal activity in response to excitatory amino acids.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
F M
FM
Faraci
K R
KR
Breese
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002560:Cerebrovascular Circulation; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008833:Microcirculation; D016202:N-Methylaspartate / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation
D011956:Receptors, Cell Surface; D009599:Nitroprusside; D009569:Nitric Oxide; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D000109:Acetylcholine; D007213:Indomethacin