U 50 488H 对高血压大鼠的利尿作用及机制

目的： 观察κ阿片受体激动剂U50 488H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U50 488H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： U50 488H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；U50 488H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，U50 488H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，U50 488H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。U50 488H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U50 488H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。

Diuretic mechanism of U 50 488H in spontaneously hypertensive rats

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50 488H decreased BP significantly in WKY rats and SHR, and the decrease of BP in SHR was more than that in WKY rats. U50 488H increased the urine volume dose-dependently in WKY rats and SHR. The urine volume of SHR increased by U50 488H was more than that of WKY rats. U50 488H (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50 488H also induced a decrease in plasma concentration of AngⅡin SHR, while it had no influence on the plasma concentration of AngⅡ in WKY rats. These effects of U50 488H were abolished by nor-BNI, a selective κ-opioid receptor antagonist. CONCLUSION: The significant decreases in plasma concentration of ADH and AngⅡmay be responsible for the effective diuresis of κ-opioid receptor stimulation by U50 488H in SHR.