Combination of chronic exercise and antihypertensive therapy enhances renoprotective effects in rats with renal ablation

BackgroundWe assessed the renal protective effects of treatment with moderate exercise (EX), with EX plus olmesartan (OLS), with EX plus azelnidipine (AZN), and with the three together in a rat model of chronic renal failure (CRF).MethodsMale 5/6-nephrectomized Wistar Kyoto (WKY) rats were divided into six groups according to the following treatments for: (i) no EX (C); (ii) moderate EX with treadmill running (20 m/min for 60 min/day, 5 days/week) (EX); (iii) EXOLS (10 mg/kg/day); (iv) EXAZN (3 mg/kg/day); (v) EXOLS (5 mg/kg/day)AZN (1.5 mg/kg/day); and (vi) sham operation (S). The rats were then treated for 12 weeks.ResultsEX, EXOLS, EXAZN, and EXOLSAZN showed decreases in the serum creatinine (Scr), an index of glomerular sclerosis (IGS), the relative interstitial volume of the renal cortex (RIV), the number of ED-1 (monoclonal antibody) positive cells (ED1 ) and the glomerular expression score of α-smooth muscle actin (α-SMA ). EXOLS, EXAZN, and EXOLSAZN blocked the development of hypertension, increased the number of Wilms' tumor-1 (WT-1) positive cells (WT1 ); EXOLS and EXOLSAZN blunted the increases in proteinuria. In particular, blood urea nitrogen (BUN), ED1 , α-SMA , WT1 , IGS, and RIV in the EXOLSAZN were the lowest among all the nephrectomized groups.ConclusionsIn the results, simultaneous treatment of EX, OLS, and AZN showed renal protective effects in this rat model suggesting that the treatment may affect the macrophage infiltration to the glomerulus, the fibroblast accumulation in the glomerulus, the mesangial activation, and the podocyte differentiation.