Sirén A L, Feuerstein G
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Neuropeptides. 1989 Nov-Dec;14(4):231-6. doi: 10.1016/0143-4179(89)90051-6.
The effects of endothelin-1 (ET-1) administered i.v. or intracerebroventricularly (i.c.v.) on arterial pressure (MAP), heart rate and cardiac output were studied in the conscious rat. Systemic injection of ET-1 (0.1 to 1 nmol/kg i.v.) increased dose-dependently MAP and decreased heart rate. The doses of 0.3 and 1 nmol/kg produced initially transient hypotension and tachycardia which were accompanied by a decrease in total peripheral resistance index (TPRI). Cardiac output was significantly reduced and TPRI increased during the pressor response to 0.3 and 1 nmol/kg ET-1. ET-1 i.c.v. (30 pmol/kg) produced a profound pressor and vasoconstrictor response which was followed by cardiovascular collapse and death within 20 min after i.c.v. injection. Low doses (1 to 10 pmol/kg) of ET-1 i.c.v. had no effect on the cardiovascular system. The present data are in accordance with the studies demonstrating biphasic blood pressure and heart rate responses to i.v. ET-1 in the rat. Profound cardiac depressor and peripheral vasoconstrictor responses were found to accompany the pressor phase. Our results also showed for the first time direct central pressor and vasoconstrictor effects of ET-1 insinuating that endothelin might be a neuropeptide participating in the central cardiovascular control.
在清醒大鼠中研究了静脉注射或脑室内注射内皮素 -1（ET-1）对动脉血压（MAP）、心率和心输出量的影响。静脉注射ET-1（0.1至1 nmol/kg）可使MAP剂量依赖性升高，并使心率降低。0.3和1 nmol/kg的剂量最初会引起短暂的低血压和心动过速，同时总外周阻力指数（TPRI）降低。在对0.3和1 nmol/kg ET-1的升压反应过程中，心输出量显著降低，TPRI升高。脑室内注射ET-1（30 pmol/kg）会产生强烈的升压和血管收缩反应，随后在脑室内注射后20分钟内出现心血管衰竭和死亡。低剂量（1至10 pmol/kg）的脑室内注射ET-1对心血管系统无影响。目前的数据与在大鼠中静脉注射ET-1时血压和心率出现双相反应的研究一致。在升压阶段发现伴有严重的心脏抑制和外周血管收缩反应。我们的结果还首次显示了ET-1直接的中枢升压和血管收缩作用，表明内皮素可能是参与中枢心血管控制的一种神经肽。
