U50 488H对高血压大鼠的利尿作用及机制  

Diuretic mechanism of U50 488H in spontaneously hypertensive rats

作　　者：郭海涛[1] 仝黎[2] 槐勇[1] 毕辉[1] 王跃民[1] 裴建明[1] 

机构地区：[1]第四军医大学基础部生理学教研室,陕西西安710032 [2]第四军医大学学员旅十四队,陕西西安710032

出　　处：《中国病理生理杂志》2007年第4期669-673,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金面上资助项目(No.30370580);全军医药卫生科研基金军队"十五"计划面上资助项目(No.01MB129)

摘　　要：目的:观察κ阿片受体激动剂U50 488H对自发性高血压大鼠(SHR)的利尿作用并探讨其作用机制。方法:用整体实验观察U50 488H对WKY大鼠和SHR血压和尿量的影响;应用放射免疫分析方法观察WKY大鼠和SHR血浆中体液因子的变化。结果:U50 488H显著降低WKY大鼠和SHR的血压,对SHR产生的降压效应大于WKY大鼠;U50 488H剂量依赖性地引起WKY大鼠和SHR尿量的增加,而且对SHR的利尿作用强于WKY大鼠;测定血浆因子水平发现,U50 488H不仅能引起WKY大鼠和SHR血浆ADH水平的显著下降,并且对SHR血浆ADH水平的降低效应大于WKY大鼠;另外,U50 488H对WKY大鼠血浆AngⅡ水平无明显影响,但可以引起SHR血浆AngⅡ水平显著下降。U50 488H的以上效应均可被选择性κ阿片受体阻断剂nor-BNI所阻断。结论:κ阿片受体激动剂U50 488H显著下调血浆中抗利尿激素和血管紧张素Ⅱ的水平可能与其引起SHR强利尿效应有关。AIM ： To investigate the diuretic effects of U 50 488 H, a selective κ - opioid receptor agonist, in spontaneously hypertensive rats （SHR） and explore their mechanism. METHODS： The physiological experimental technique was used to measure the blood pressure （ BP）, and the volume of urine output in normatensive WKY （ Wistar - Kyoto） rats and SHR was measured. The plasma levels of some humoral factors were detected by radioimmunoassay. RESULTS： U 50 488H decreased BP significantly in WKY rats and SHR, and the decrease of BP in SHR was more than that in WKY rats. U 50 488H increased the urine volume dose - dependently in WKY rats and SHR. The urine volume of SHR increased by U 50 488H was more than that of WKY rats. U 50 488H （ 1 mg/kg） produced marked decrease in plasma concentration of ADH in WKY rats and SHR, and the decrease in SHR was significantly stronger than that in WKY. U 50 488H also induced a decrease in plasma concentration of Ang Ⅱ in SHR, while it had no influence on the plasma concentration of Ang Ⅱ in WKY rats. These effects of U 50 488H were abolished by nor - BNI, a selective κ - opioid receptor antagonist. CONCLUSION： The significant decreases in plasma concentration of ADH and Ang Ⅱ may be responsible for the effective diuresis of κ - opioid receptor stimulation by U 50 488H in SHR.

关 键 词：利尿 血管升压素类 血管紧张素Ⅱ 受体 阿片样 κ 

分 类 号：R544.1[医药卫生—心血管疾病]