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 stimulation and nicotine of cerebral artery strips without endothelium were abolished by tetrodotoxin and hexamethonium, respectively. N(G)-nitro-L-arginine, 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 stimulation and nicotine. However, in the strips treated with diethyldithiocarbamate, an inhibitor of copper/zinc superoxide dismutase (SOD), the responses were significantly inhibited by duroquinone. The inhibition was partially reversed by SOD. Physostigmine inhibited, but atropine potentiated, the neurogenic response. The relaxation was attenuated by acetylcholine but not by VIP. There were nerve fibers and bundles containing NADPH diaphorase in the adventitia of cerebral arteries. It appears that porcine cerebral arteries are innervated by NO synthase-containing nerves that liberate NO on excitation as a neurotransmitter to produce muscular relaxation, and the nerve function is protected by endogenous SOD from degradation of NO by superoxide anions. The neurogenic relaxation is inhibited by acetylcholine released from cholinergic nerves, possibly because of an impaired production or release of NO.
Tanaka
T
T
Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu, Japan.
Okamura
T
T
Handa
J
J
Toda
N
N
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D016227:Benzoquinones; D005731:Ganglionic Stimulants; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine; D013482:Superoxide Dismutase; D000109:Acetylcholine; C034257:duroquinone; D009638:Norepinephrine