Okamura T, Enokibori M, Toda N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
J Pharmacol Exp Ther. 1993 Sep;266(3):1416-21.
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.
尼古丁可使去除内皮的犬颞浅动脉条产生短暂收缩，随后出现双相（快速和缓慢）舒张。六甲铵处理可消除对尼古丁的反应。酚妥拉明可消除尼古丁诱导的收缩，而一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NA）可增强该收缩。吲哚美辛和前列腺素I2合成酶抑制剂反苯环丙胺可显著抑制缓慢出现的舒张，而L-NA可消除快速舒张。L-精氨酸可逆转L-NA的抑制作用，而D-精氨酸则无此作用。NG-硝基-D-精氨酸无作用。经壁电刺激可使酚妥拉明处理的动脉产生短暂舒张。该舒张不受吲哚美辛影响，但可被L-NA和河豚毒素消除。尼古丁可使去除内皮的动脉细胞内的环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）增加。吲哚美辛可抑制cAMP的增加，但L-NA无此作用；而吲哚美辛不影响cGMP的增加，但L-NA可消除其增加。可以得出结论，尼古丁刺激支配颞动脉壁的肾上腺素能神经和一氧化氮能神经，分别导致收缩和快速出现的舒张；后者由cGMP介导。一氧化氮合酶抑制剂对尼古丁收缩反应的增强作用可能是对神经源性一氧化氮介导的舒张的抑制。尼古丁引起的缓慢舒张似乎与可能由内皮下单神经元组织释放的前列腺素I2产生的cAMP升高有关。
