Effects of exercise training on renal interstitial fibrosis and renin-angiotensin system in rats with chronic renal failure.

Abstract

To clarify the mechanisms of the renal protective effects of exercise training, we examined the effects of exercise training on the renal interstitial fibrosis and renin-angiotensin system (RAS) in rats with chronic renal failure. Six-week-old male Sprague-Dawley rats were divided into three groups: sham operation; 5/6 nephrectomy + sedentary; 5/6 nephrectomy + exercise training. The 5/6 nephrectomy + exercise training group underwent treadmill running (20 m/min, 60 min/day, 5 days/week). After 12 weeks, renal function, histology and protein expression of collagen type I, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinase (TIMP) and RAS components in the renal cortex were examined. Exercise training ameliorated the 5/6 nephrectomy-induced hypertension, proteinuria, renal dysfunction, glomerular sclerosis and renal interstitial fibrosis. 5/6 Nephrectomy increased the expression of collagen type I, TGF-β1, MMP-2, MMP-9, TIMP-1, angiotensinogen, angiotensin-converting enzyme (ACE), (pro)renin receptor and angiotensin II type 1 receptor, and exercise training inhibited the 5/6 nephrectomy-increased expression of collagen type I, TGF-β1, TIMP-1, angiotensinogen and ACE expressions. 5/6 Nephrectomy decreased the expression of renin, ACE2, angiotensin II type 2 receptor and Mas receptor, and exercise training inhibited the 5/6 nephrectomy-decreased expressions. These results indicated that exercise training attenuates the progression of glomerular sclerosis and renal interstitial fibrosis in chronic renal failure rats. The renal protective effects of exercise training may be mediated by ameliorating the renal collagen turnover and the exacerbation of renal RAS.