乙醇及其他脂肪族醇类对大鼠肛门尾骨肌和胃底条带中一氧化氮介导的舒张作用。

Effects of ethanol and other aliphatic alcohols on NO-mediated relaxations in rat anococcygeus muscles and gastric fundus strips.

作者信息

Rand M J, Li C G

机构信息

Department of Pharmacology, University of Melbourne, Victoria, Australia.

出版信息

Br J Pharmacol. 1994 Apr;111(4):1089-94. doi: 10.1111/j.1476-5381.1994.tb14856.x.

DOI:10.1111/j.1476-5381.1994.tb14856.x

PMID:8032595

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1910133/

Abstract

In anococcygeus muscles, ethanol (20-500 mM) slightly increased the tone and inhibited relaxations elicited by nitrergic nerve stimulation (0.5-5 Hz) in a concentration-dependent manner. 2. Other aliphatic alcohols decreased the tone but had inhibitory effects similar to ethanol on stimulation-induced relaxations, the EC50 (mM) values being: methanol 280, ethanol 80, propan-1-ol 20, propan-2-ol 55, propan 1,2-diol 135, butan-1-ol 120, butan-2-ol 15 and pentan-1-ol 3. 3. Relaxations induced by sodium nitroprusside (SNP, 10 nM) were inhibited by ethanol (20-500 mM) in a concentration-dependent manner and by propan-2-ol (100 mM). Relaxations induced by NO (1 microM) were inhibited by high concentrations of ethanol (200-300 mM) and by propan-2-ol (100 mM). 4. In gastric fundus strips, ethanol (60-200 mM) did not affect the resting tone but inhibited NO-mediated relaxations elicited by low frequency (1 Hz) field stimulation and reduced the initial relaxation by high frequency field stimulation (10 Hz) and by SNP (50 nM). The relaxant action of isoprenaline (10 nM) was not reduced although it was slightly slower in onset. Other aliphatic alcohols tested decreased the tone and inhibited relaxations elicited by field stimulation. 5. Acetaldehyde (1-10 mM) inhibited relaxations elicited by field stimulation and SNP in both the rat anococcygeus muscles and gastric fundus strips. The tone of gastric fundus strips was decreased by acetaldehyde but it was transiently increased in anococcygeus muscles. 6. The dehydrogenase inhibitors, 4-methylpyrazole (100 MicroM) and disulfiram (100 MicroM) did not significantly affect the inhibition by ethanol of nitrergic nerve stimulation-induced relaxations in anococcygeus muscles, which suggests that ethanol acts directly.7. The inhibition of NO-mediated relaxations by alcohols is attributed to sequestration of NO to form nitroso-alcohols.

摘要

在尾骨肌中，乙醇（20 - 500 mM）可轻微增加肌张力，并以浓度依赖性方式抑制由氮能神经刺激（0.5 - 5 Hz）引起的舒张。2. 其他脂肪醇可降低肌张力，但对刺激诱导的舒张具有与乙醇相似的抑制作用，其半数有效浓度（EC50，mM）值分别为：甲醇280、乙醇80、丙醇-1 20、丙醇-2 55、1,2-丙二醇135、丁醇-1 120、丁醇-2 15和戊醇-1 3。3. 硝普钠（SNP，10 nM）诱导的舒张以浓度依赖性方式被乙醇（20 - 500 mM）和丙醇-2（100 mM）抑制。一氧化氮（NO，1 microM）诱导的舒张被高浓度乙醇（200 - 300 mM）和丙醇-2（100 mM）抑制。4. 在胃底条中，乙醇（60 - 200 mM）不影响静息肌张力，但抑制低频（1 Hz）电场刺激引起的NO介导的舒张，并降低高频电场刺激（10 Hz）和SNP（50 nM）引起的初始舒张。异丙肾上腺素（10 nM）的舒张作用虽起效稍慢但未减弱。所测试的其他脂肪醇可降低肌张力并抑制电场刺激引起的舒张。5. 乙醛（1 - 10 mM）在大鼠尾骨肌和胃底条中均抑制电场刺激和SNP引起的舒张。胃底条的肌张力被乙醛降低，但在尾骨肌中则短暂升高。6. 脱氢酶抑制剂4-甲基吡唑（100 microM）和双硫仑（100 microM）对乙醇抑制尾骨肌中氮能神经刺激诱导的舒张无显著影响，这表明乙醇直接起作用。7. 醇类对NO介导的舒张的抑制作用归因于NO被螯合形成亚硝基醇。