Exercise training (Ex) is known to have antihypertensive and renal protective effects in humans and animals, but the mechanisms of these effects were unclear. Renin-angiotensin system (RAS) is associated with progression of hypertension and kidney diseases. To clarify the mechanisms of renal protective effects of Ex, the present study examined the effects of Ex on renal damage and RAS in the kidney of rats with chronic renal failure (CRF).

Six-week-old male Sprague-Dawley rats were divided into three groups: (1) sham operation; (2) 5/6 nephrectomy (Nx)+sedentary; (3) Nx+Ex with treadmill running (20m/min, 60min/day, 5days/week) for 12weeks. Systolic blood pressure (SBP) and urinary excretion of protein (UP) were measured every 2weeks. The index of glomerular sclerosis (IGS), the relative interstitial volume of the renal cortex (RIV) and area of renal fibrosis (RF) were examined by using histological analyses. Protein expression of transforming growth factor (TGF)-β1 and RAS components in the renal cortex were examined by western blot.

Nx increased the SBP, UP and serum creatinine, but Ex decreased SBP after 8 weeks, UP after 10weeks and serum creatinine at 12weeks. Histological analysis revealed that Nx increased IGF, RIV, RF (IGS: 0.05±0.01 vs. 2.59±0.01, RIV: 4.6±0.7 vs. 19.7±0.7%, RF: 10.1±1.7 vs. 26.9±1.5%), but these parameter was improved by EX (IGS: 1.96±0.03, RIV: 12.5±1.0%, RF: 19.4±0.4%). Nx increased TGF-β1, angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) expressions, and Ex inhibited the Nx-increased expressions in the renal cortex. Nx decreased renin and angiotensin II type 2 receptor (AT2R) expressions, and Ex inhibited the Nx-decreased expressions in the renal cortex.

Ex attenuated the progression of hypertension, glomerular sclerosis, and renal fibrosis in CRF rats. The antihypertensive and renal protective effects of Ex may be mediated by ameliorating the exacerbation of renal RAS.