Modifications by superoxide-generating agent, neurotransmitters and neuromodulators of nitroxidergic nerve function in monkey cerebral arteries.

Isolated monkey cerebral arteries denuded of the endothelium responded to transmural electrical stimulation (5 Hz for 40 sec) with relaxations that are mediated by nitric oxide (NO) synthesized from L-arginine. The relaxant response was slightly inhibited by duroquinone, a superoxide anion-generating agent. The agent markedly inhibited the response after treatment with diethylthiocarbamic acid, an inhibitor of copper/zinc superoxide dismutase. The inhibition was partially reversed by superoxide dismutase. The neurogenic relaxation was reduced by acetylcholine acting on prejunctional muscarinic receptors. Neuropeptide Y, morphine, ATP, clonidine and pituitary adenylate cyclase-activating polypeptide did not change the response to nerve stimulation. Sodium nitroprusside in a dose sufficient to produce relaxation attenuated the neurogenic response. It is concluded that the neurotransmitter liberated from vasodilator nerves in monkey cerebral arteries is free NO rather than a stable analog of NO, like S-nitrosocysteine. Substances other than acetylcholine released as neuromodulators do not seem to regulate the NO-mediated nerve function.