Savci V, Ulus I H
Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey.
J Cardiovasc Pharmacol. 1997 Nov;30(5):667-75. doi: 10.1097/00005344-199711000-00018.
The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 microg; i.c.v.) pretreatment prevented the pressor and bradycardic responses to choline, whereas atropine (10 microg; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pressor responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 microg; i.c.v.), a high-affinity neuronal choline-uptake inhibitor. Plasma vasopressin levels of endotoxin-treated rats were severalfold higher than those of control animals, and choline (50-150 microg; i.c.v.) produced further increases in plasma vasopressin in this condition. Mecamylamine abolished vasopressin response to endotoxin as well as to choline. The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.
在经内毒素处理的大鼠中研究了脑室内注射胆碱的心血管效应。静脉注射内毒素（20mg/kg）在治疗后10分钟内引起中度低血压和心动过速。在此情况下，胆碱（50、100和150微克；脑室内注射）以剂量依赖方式升高血压并降低心率。美加明（50微克；脑室内注射）预处理可预防对胆碱的升压和心动过缓反应，而阿托品（10微克；脑室内注射）未能改变这两种反应。单独的阿托品预处理可抑制内毒素诱导的低血压。用高亲和力神经元胆碱摄取抑制剂半胱氨酸3（20微克；脑室内注射）预处理可减弱经内毒素处理的大鼠对胆碱的升压反应。经内毒素处理的大鼠血浆血管加压素水平比对照动物高几倍，在此情况下，胆碱（50 - 150微克；脑室内注射）使血浆血管加压素进一步升高。美加明消除了对内毒素以及对胆碱的血管加压素反应。在胆碱注射5分钟后静脉注射血管加压素受体拮抗剂（β-巯基-β，β-环亚戊基丙酰基(1)-O-甲基-Tyr2，Arg8）血管加压素（10微克/千克）可使血压从升高水平降至胆碱注射前水平，但未改变心动过缓。这些结果表明，在内毒素处理的大鼠中，胆碱通过导致中枢烟碱胆碱能途径激活的突触前机制升高血压并降低心率。血浆血管加压素水平的升高似乎参与了对胆碱的升压反应，但未参与心动过缓反应。
