Doursout M F, Chelly J E, Liang Y Y, Buckley J P
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030.
Clin Exp Hypertens A. 1992;14(3):393-411. doi: 10.3109/10641969209036197.
The present study investigated the role of ouabain-dependent inhibition of the Na(+)-K+ pump and stimulation of the brain renin-angiotensin system by looking at 1) the short-term and long-term effects of ouabain on arterial blood pressure, and 2) the acute and chronic effects of angiotensin II (ANG II) intraventricularly (i.c.v.) on the release of an endogenous inhibitor of the Na(+)-K+ pump. Ouabain infused subcutaneously in a dose of 1.5 mg.kg-1. 24 h-1 for 7 days did not affect arterial blood pressure in rats, whereas increases in both blood pressure and weight were observed in rats infused with ouabain at the same dose for a 4-week period. Plasma supernate obtained from pentobarbital-anesthetized dogs acutely treated with ANG II (1 microgram i.c.v. every 30 min for 2 h) induced a 44% decrease in the ouabain-sensitive 86Rb uptake by the rat tail artery which was prevented by pretreatment with saralasin i.c.v. Plasma supernate obtained from dogs that were infused for 4 days with ANG II (20 ng/min i.c.v.) and received saline as the drinking fluid also reduced by 34% the ouabain-sensitive 86Rb uptake by the rat tail artery. The present study provides evidence that chronic inhibition of the Na(+)-K+ pump for 4 weeks leads to the development of hypertension and that the release of an endogenous inhibitor of the Na(+)-K+ pump is implicated in the hypertension resulting from chronic stimulation of the brain angiotensin-system and an increase in sodium chloride intake.
本研究通过观察以下两方面来探究哇巴因对钠钾泵的依赖性抑制作用以及对脑肾素 - 血管紧张素系统的刺激作用：1）哇巴因对动脉血压的短期和长期影响；2）脑室内注射血管紧张素 II（ANG II）对钠钾泵内源性抑制剂释放的急性和慢性影响。以1.5 mg·kg⁻¹·24 h⁻¹的剂量皮下注射哇巴因，持续7天，对大鼠的动脉血压没有影响，而以相同剂量注射哇巴因4周的大鼠，血压和体重均有所增加。从经戊巴比妥麻醉的犬体内获取血浆上清液，这些犬经ANG II急性处理（每30分钟脑室内注射1微克，共2小时），导致大鼠尾动脉对哇巴因敏感的⁸⁶Rb摄取量减少44%，而脑室内预先注射沙拉新可预防这种情况。从连续4天脑室内注射ANG II（20 ng/min）并饮用生理盐水的犬体内获取的血浆上清液，也使大鼠尾动脉对哇巴因敏感的⁸⁶Rb摄取量减少了34%。本研究提供了证据，表明钠钾泵长期抑制4周会导致高血压的发生，并且钠钾泵内源性抑制剂的释放与慢性刺激脑肾素 - 血管紧张素系统及氯化钠摄入量增加所导致的高血压有关。
