Neurogenic and non-neurogenic relaxations caused by nicotine in isolated dog superficial temporal artery.
Nicotine produced a transient contraction followed by biphasic (rapid and slow) relaxations in dog superficial temporal arterial strips denuded of the endothelium. The responses to nicotine were abolished by treatment with hexamethonium. The nicotine-induced contraction was abolished by phentolamine and potentiated by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor. The slowly developing relaxation was markedly suppressed by indomethacin and tranylcypromine, a prostaglandin I2 synthetase inhibitor, whereas the rapid relaxation was abolished by L-NA. The inhibitory effect of L-NA was reversed by L-, but not D-, arginine. NG-nitro-D-arginine had no effect. Transmural electrical stimulation elicited a transient relaxation in phentolamine-treated arteries. The relaxation was not influenced by indomethacin but was abolished by L-NA and tetrodotoxin. Nicotine increased intracellular cyclic AMP and cyclic GMP in the endothelium-denuded arteries. The increment of cyclic AMP was inhibited by indomethacin but not by L-NA, whereas that of cyclic GMP was not influenced by indomethacin but was abolished by L-NA. It may be concluded that nicotine stimulates the adrenergic and nitroxidergic nerves innervating the temporal arterial wall, resulting in a contraction and a rapidly developing relaxation, respectively; the latter is mediated by cyclic GMP. Potentiation by the nitric oxide synthase inhibitor of the contractile response to nicotine is expected to be a suppression of the relaxation mediated by the nerve-derived nitric oxide. Slow relaxations caused by nicotine appear to be associated with the elevation of cyclic AMP produced possibly by prostaglandin I2, which is released from subendothelial, non-neuronal tissues.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Enokibori
M
M
Toda
N
N
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D013699:Temporal Arteries / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism
D019335:Nitroarginine; D009569:Nitric Oxide; D009538:Nicotine; D001120:Arginine; D015237:Dinoprost; D006152:Cyclic GMP