恶性高血压大鼠肾脏肾上腺髓质素受体表达及利尿剂干预作用

Expression of renal adrenomedullin receptor system in the severely hypertension rat and the effect of diuretic on it

目的:探讨肾上腺髓质素(AM)受体系统在恶性高血压大鼠肾脏中的病理生理作用及利尿剂的干预作用。方法:实验分3组:Wistar-Kyoto大鼠(WKY)为对照组,有卒中倾向的自发性高血压大鼠组(SHR-SP),用三氯甲噻嗪治疗8周组(SHR-SP+Diuretic)。通过放射性免疫分析,检测AM受体系统如降钙素受体类似受体(CRLR),受体活性修饰蛋白(RAMP)2和RAMP3的基因表达水平。结果:SHR-SP组血压,血中神经体液因子均较WKY组有所升高,而肾功能有所降低。肾脏的皮质中CRLR,RAMP2,RAMP3的 mRNA水平显著高于WKY组。长期的利尿治疗能降低血压,伴随血液和肾脏组织中AM受体系统降低而改善肾功能,提高神经体液因子浓度。结论:在循环血液和肾脏组织中,AM受体系统的上调可能参与恶性高血压大鼠的病理生理过程,利尿剂可以下调AM受体。

Objective： To investigate the pathophysiological role of the renal adrenomedullin （AM） receptor system in severe hypertensive rats and the effect of diuretic on it. Method： The following three groups were studled： control Wistar Kyoto rats （WKY）, spontaneously hypertensive stroke-prone rats （SHR-SP）, and 8 weeks trichlormethiazide-treated SHR-SP. Gene expression levels of AM receptor system components such as calcitonin receptor-like receptor （CRLR）, receptor-activity modifying protein （RAMP）2 and RAMP3 were measured by immunoradiometric assay. Result：SHR-SP had increased blood pressure, plasma neurohumoral factors, and lower renal function than WKY. The mRNA levels of CRLR, RAMP 2, and RAMP3 in the renal cortex were higher in SHR-SP than in WKY. Chronic diuretic treatment decreased blood pressure and improved kidney function and neurohumoral factors, with reductions in plasma and renal AM receptor system. Conclusion： Up regulation of circulating and renal AM receptor system may modulate the pathophysiological process in SHR-SP and diuretic could inhibit the AM receptors.