Effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats / 中华肾脏病杂志

ABSTRACT

ObjectiveTo investigate whether aldosterone infusion induces glomerular or podocyte injury in rats and to evaluate the effects of eplerenoen (EPL), andodipine (CCB) and telmisartan (ARB) on aldosterone- induced injury. MethodsThirty male Sprague-Dawley rats were divided into 5 groups control, subcutaneous infusion of aldosterone (1.5 μg/h, ALD group) and aldosterone infusion plus eplerenone (100 mg·kg-1·d-1, EPL group), amlodipine(10 nag·kg-1·d-1 CCB group), telmisartan (3 mg·kg-1·d-1, ARB group), respectively. Systolic blood pressure(SBP) and urinary albumin excretion ratio(UAER) were measured at day 0, 7, 14, 21, 28. Blood samples were harvested to detect plasma angiotensin Ⅱ, plasma aldosterone, serum sodium, serum potassium and serum creatinine at day 28. Glomerular damge was quantified by morphological glomerular injury score (GIS). Immunohistochemistry and RT-PCR were performed to evaluate podocyte lesion, and apoptosis ratio of pedocyte (ARP) in a glomerular cross section was analyzed by TUNEL. ResultsALD infusion progressively increased SBP and UAER compared with CTL (P＜0.01). SBP was significantly reduced in EPL, CCB or ARB-treated animals, meanwhile, UAER was decreased in EPL and ARB group, but not in CCB group. The ALD-infused rats exibited hypernatremia and hypopotassaemia, which were blocked by EPL adminstration but not by CCB or ARB treatment. ARB group had a significant increase in plasma angiotensin Ⅱ compared with ALD, CCB and EPL groups(P＜0.01). The ALD-infused animals developed hyperaldosteronemia compared with CTL, but with no difference of plasma aldosterone among ALD, EPL, CCB and ARB-treated rats. Treatment with EPL prevented an increase of GIS and ARP compared with CCB and ARB (P＜0.05, P＜0.01). Protein and mRNA expression of nephfin was up-regulated in ALD group (P＜ 0.01), but was significantly prevented by EPL treatment(P＜0.01), whereas CCB and ARB therapy had no such effect. Conclusion ALD infusion significantly induces glomerular and pedocyte injury which is blocked by EPL but not by CCB or ARB independently on systemic hemodynamics.