Effects of imidapril treatment on aquaporin-2 expression in the kidneys and excretion in the urine of hypertensive rats

咪达普利治疗对高血压大鼠肾脏中水通道蛋白-2表达及尿液排泄的影响

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Abstract

Renal aquaporin-2 (AQP2) is critical for maintaining water balance and is associated with hypertension. Anti-hypertensive drugs, including imidapril, improve kidney function; however, it remains unclear whether these effects are mediated through the regulation of AQP2. In this study, the effects of imidapril on AQP2 expression in the kidneys and excretion in urine were assessed in hypertensive rats. Hypertension was induced in 24 rats, which were randomized into a control group, treated with water only, and an imidapril treatment group (n=12 per group). Blood and urine samples were collected from all rats to determine blood pressure (BP), serum Na(+), urine volume and urine osmolality after 8 weeks of treatment. Molecular and immunological techniques were used to measure the expression of AQP2 in the kidneys. Urine AQP2 concentration was detected by indirect enzyme-linked immunosorbent assay (ELISA). The concentration of plasma arginine vasopressin (AVP), a regulator of AQP2 was detected by radioimmunoassay (RIA). Hypertensive rats treated with imidapril exhibited reduced BP and 24-h urine osmolality, with a concomitant increase in 24-h urine volume, compared with control hypertensive rats (P<0.05). Additionally, the expression of Aqp2 mRNA, detected by RT-PCR, and AQP2 protein, detected by immunohistochemistry and western blotting, in renal tissue significantly decreased (P<0.05). Finally, urine AQP2 concentration increased while plasma AVP concentration decreased following imidapril treatment (P<0.05). These findings indicate that imidapril reduces the expression level of AQP2 in renal tissue and accelerates its excretion.

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