Nitric oxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries.
Helical strips of bovine basilar arteries denuded of the endothelium responded to transmural electrical stimulation with frequency-dependent relaxations that were abolished or markedly attenuated by treatment with tetrodotoxin, oxyhemoglobin and Methylene Blue. Relaxations induced by vasoactive intestinal polypeptide and calcitonin gene-related peptide were not affected by oxyhemoglobin and Methylene Blue. The neurally induced relaxation was not attenuated in the artery made unresponsive to these peptides by successive application. The relaxation caused by nerve stimulation was markedly inhibited by treatment with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, which did not inhibit the relaxation caused by exogenously applied nitric oxide. The inhibition was reversed by L-arginine but not by the D-enantiomer. Exogenously applied acetylcholine did not alter the tone of endothelium-denuded arteries. Neurally induced relaxations were attenuated by treatment with acetylcholine and physostigmine and were significantly potentiated by atropine. It may be concluded that the relaxation induced by nerve stimulation is mediated by nitric oxide, but not by vasoactive intestinal polypeptide or calcitonin gene-related peptide, derived from vasodilator nerves innervating the bovine basilar artery, and the nerve function is inhibited prejunctionally via muscarinic receptor activation by acetylcholine released from cholinergic nerves but is not influenced by vasoactive intestinal polypeptide.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
Toda
N
N
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010830:Physostigmine / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; D009479:Neuropeptides; D019335:Nitroarginine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D001120:Arginine; D010830:Physostigmine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine