Whittle B J, Payne A N, Esplugues J V
Department of Pharmacology, Wellcome Research Laboratories, Kent, England.
J Cardiovasc Pharmacol. 1989;13 Suppl 5:S103-7; discussion S123. doi: 10.1097/00005344-198900135-00026.
The cardiovascular and bronchoconstrictor actions of endothelin-1 (ET-1) in the anesthetized guinea pig and the cardiovascular effects and gastric ulcerogenic actions in the anesthetized rat were investigated. In the guinea pig, ET-1 (0.05-1 nmol/kg i.v.) induced a dose-related increase in pulmonary inflation pressure, which was substantially inhibited by pretreatment with indomethacin and the thromboxane receptor antagonist BM 13.177. The concurrent vasopressor effects of ET-1 were attenuated but not abolished by these agents. In the rat, ET-1 (0.1-0.4 nmol/kg i.v.) induced a biphasic effect on arterial blood pressure (BP), with a transient fall being followed by a rise, which was unaffected by indomethacin pretreatment, whereas i.v. infusion of ET-1 induced only an increase in BP. Local intra-arterial infusion of ET-1 (0.04-0.1 nmol/kg/min) induced extensive macroscopically determined gastric mucosal damage in the rat, confirmed histologically. Thus, the pharmacological profile of ET-1 encompasses bronchoconstriction, vasopressor and vasodepressor actions, as well as potent gastric ulcerogenic properties.
研究了内皮素 -1（ET -1）在麻醉豚鼠体内的心血管和支气管收缩作用，以及在麻醉大鼠体内的心血管效应和致胃溃疡作用。在豚鼠中，ET -1（静脉注射0.05 - 1 nmol/kg）可引起肺充气压力呈剂量相关增加，吲哚美辛和血栓素受体拮抗剂BM 13.177预处理可显著抑制该作用。这些药物可减弱但不能消除ET -1同时产生的升压作用。在大鼠中，ET -1（静脉注射0.1 - 0.4 nmol/kg）对动脉血压（BP）产生双相效应，先是短暂下降，随后上升，吲哚美辛预处理对此无影响，而静脉输注ET -1仅引起血压升高。局部动脉内输注ET -1（0.04 - 0.1 nmol/kg/min）在大鼠中引起广泛的肉眼可见的胃黏膜损伤，经组织学证实。因此，ET -1的药理学特性包括支气管收缩、升压和降压作用，以及强大的致胃溃疡特性。
