Neurogenic vasodilation mediated by nitric oxide in porcine cerebral arteries

Mechanisms of neurogenic vasodilatation and its modification by superoxide, acetylcholine, and vasoactive intestinal peptide (VIP) in porcine cerebral arteries were investigated. Relaxant responses to transmural electrical st imulation and nicotine of cerebral artery strips without endothelium were a bolished by tetrodotoxin and hexamethonium, respectively. N-G-nitro-L-argin ine, a nitric oxide (NO) synthase inhibitor, abolished or markedly reduced the neurogenic response but did not affect the relaxation by exogenous NO. The inhibitory effect was reversed by L-arginine. Duroquinone, a superoxide -generating agent, did not alter the relaxations induced by electrical stim ulation and nicotine. However, in the strips treated with diethyldithiocarb amate, an inhibitor of copper/zinc superoxide dismutase (SOD), the response s were significantly inhibited by duroquinone. The inhibition was partially reversed by SOD. Physostigmine inhibited, but atropine potentiated, the ne urogenic response. The relaxation was attenuated by acetylcholine but not b y VIP. There were nerve fibers and bundles containing NADPH diaphorase in t he adventitia of cerebral arteries. It appears that porcine cerebral arteri es are innervated by NO synthase-containing nerves that liberate NO on exci tation as a neurotransmitter to produce muscular relaxation, and the nerve function is protected by endogenous SOD from degradation of NO by superoxid e anions. The neurogenic relaxation is inhibited by acetylcholine released from cholinergic nerves, possibly because of an impaired production or rele ase of NO.