Mosqueda-Garcia R, Kunos G
Department of Pharmacology, McGill University, Montreal, Que., Canada.
Brain Res. 1988 Feb 23;442(1):119-23. doi: 10.1016/0006-8993(88)91438-2.
The cardiovascular effects of clonidine and their inhibition by naloxone or naloxone methylbromide were tested in urethane-anesthetized, normotensive Sprague-Dawley rats. Clonidine administered intravenously (5 micrograms/kg) or directly into the nucleus tractus solitarii (NTS, 5 nmol) caused hypotension and bradycardia. The effects of intra-NTS clonidine were dose-dependently inhibited by intra-NTS administration of either antagonist, naloxone being 10 times more potent than naloxone methylbromide. The effects of i.v. clonidine were significantly inhibited by 2 mg/kg of i.v. naloxone, but were unaffected by 20 mg/kg of i.v. naloxone methylbromide. Naloxone alone had no effect on blood pressure or heart rate when given either centrally or systemically, whereas naloxone methylbromide given i.v., but not intra-NTS, caused transient hypotension and tachycardia. It is concluded that central but not peripheral opiate receptors are involved in the cardiovascular effects of clonidine.
在经乌拉坦麻醉的正常血压斯普拉格-道利大鼠中，测试了可乐定的心血管效应以及纳洛酮或甲基溴化纳洛酮对其的抑制作用。静脉注射可乐定（5微克/千克）或直接注入孤束核（NTS，5纳摩尔）会导致低血压和心动过缓。NTS内给予任何一种拮抗剂，均可剂量依赖性地抑制NTS内可乐定的作用，纳洛酮的效力比甲基溴化纳洛酮强10倍。静脉注射2毫克/千克的纳洛酮可显著抑制静脉注射可乐定的作用，但静脉注射20毫克/千克的甲基溴化纳洛酮则无此作用。单独给予纳洛酮，无论是中枢给药还是全身给药，对血压或心率均无影响，而静脉注射甲基溴化纳洛酮（而非NTS内给药）会引起短暂的低血压和心动过速。得出的结论是，中枢而非外周阿片受体参与了可乐定的心血管效应。
