Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy

Objectives We assessed the renal and peripheral effects of chronic exercise in a rat model of diabetic nephropathy and the benefits of combined exercise and losartan. Methods Heminephrectomized Goto-Kakizaki rats were divided into four groups: (i) no exercise ( control); (ii) exercise with treadmill running; (iii) losartan; (iv) exercise plus losartan, and the rats were treated for 12 weeks. Results Losartan and exercise plus losartan significantly decreased systolic blood pressure (SBP). Exercise, exercise and losartan, and losartan blunted the increases in proteinuria. The index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex were significantly improved in the exercise, exercise and losartan, and losartan groups. The IGS, expressions of ED-1 and alpha-smooth muscle actin in the glomerulus were the lowest, and the number of Wilms' tumour was the highest in the exercise plus losartan group. The endurance, the proportion of type I fibre and capillarization in the extensor digitorum longus muscle were greater in the trained groups. Conclusion These results suggest that both exercise and losartan have renoprotective effects, and the combination of exercise and losartan provided greater renoprotective effects than losartan alone, and may affect macrophage infiltration, mesangial activation, and podocyte loss in this model of diabetic nephropathy. It is also suggested that exercise has a specific renoprotective effect that is not related to SBP reduction, and can enhance endurance without renal complications.