In patients with chronic kidney disease, exercise training with moderate intensity protects renal function and improves mortality. However, the mechanisms of the renal protective effects of exercise training in chronic kidney disease have not been clarified. This study investigated the effects of exercise training on renal NADPH oxidative and xanthine oxidase, which are major sources of reactive oxygen species, in rats with chronic renal failure. Six-week-old, male Sprague–Dawley rats were divided into the sham operation, 5/6 nephrectomy (Nx)+ sedentary, and Nx+ exercise training groups. The Nx+ exercise training group underwent treadmill running. After 12 weeks, systolic blood pressure, renal function, malondialdehyde, renal NADPH oxidase, and xanthine oxidase were examined. Nx induced hypertension, proteinuria, and renal dysfunction, and exercise training attenuated these disorders. Although the plasma levels of malondialdehyde were not different among the group, urinary levels were increased by Nx and decreased by exercise training. Renal activity and expression of NADPH oxidase and xanthine oxidase were increased by Nx and decreased by exercise training. These results indicate that exercise training attenuates hypertension and renal dysfunction and ameliorates NADPH oxidase and xanthine oxidase in rats with chronic renal failure, suggesting that the reduction of reactive oxygen species generation may be involved in the renal protective effects of exercise training.

Chronic exercise (Ex) exerts antihypertensive and renoprotective effects in rats fed a high fructose diet (HFr). To elucidate the mechanisms, the impacts of an HFr and Ex on the nitric oxide (NO) system and oxidative stress in the kidney were examined. Rats were fed a control diet or an HFr, and a part of the HFr-fed rats underwent treadmill running for 12 weeks. The HFr did not affect nitrate/nitrite (NO_x) levels in plasma and urine, and Ex increased the NO_x levels. The HFr increased thiobarbituric acid reactive substance (TBARS) levels in plasma and urine, and Ex decreased the HFr-increased TBARS levels in plasma. The HFr increased the neuronal and endothelial NO synthase (nNOS and eNOS) expressions, and Ex enhanced the HFr-increased eNOS expression. The HFr inhibited the eNOS phosphorylation at serine 1177, and Ex restored the HFr-inhibited eNOS phosphorylation. The HFr increased xanthine oxidase and NADPH oxidase activities, and Ex restored the HFr-increased xanthine oxidase activity but enhanced the HFr-increased NADPH oxidase activity. The HFr increased the nitrotyrosine levels, and Ex attenuated the HFr-increased levels. These results indicate that although Ex enhances the HFr-increased eNOS expression and NADPH oxidase activity, an HFr inhibits renal eNOS phosphorylation and NO bioavailability, whereas Ex ameliorates them.

Introduction: High-fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) has antihypertensive and renal protective effects in rats fed HFr; however, there has been little discussion about the DS rats, which exhibit metabolic disturbances. This study thus examined the effects of Ex on DS rats fed HFr. Methods: Male DS rats were divided into three groups. The control group was fed a control diet, and both the HFr group and the HFr–Ex group were fed an HFr (60% fructose). The HFr–Ex group also underwent treadmill running (20 m·min⁻¹, 60 min·d⁻¹, 5 d·wk⁻¹). After 12 wk, renal function, histology, and renin–angiotensin system were examined. Results: HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor, and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type 2 receptor, and Mas receptor, and Ex restored the ACE2 and Mas receptor expressions to the control levels and further decreased the angiotensin II type 2 receptor expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels. Conclusions: Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal renin–angiotensin system may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.

Introduction: Polycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. The effects of chronic exercise on the progression of PKD were investigated in a polycystic kidney (PCK) rat model. Methods: Six-week-old male PCK rats were divided into a sedentary group and an exercise group. The exercise group underwent forced treadmill exercise for 12 wk (28 m·min⁻¹, 60 min·d⁻¹, 5 d·wk⁻¹). After 12 wk, renal function and histology were examined, and signaling cascades of PKD progression, including arginine vasopressin (AVP), were investigated. Results: Chronic exercise reduced the excretion of urinary protein, liver-type fatty acid–binding protein, plasma creatinine, urea nitrogen, and increased plasma irisin and urinary AVP excretion. Chronic exercise also slowed renal cyst growth, glomerular damage, and interstitial fibrosis and led to reduced Ki-67 expression. Chronic exercise had no effect on cAMP content but decreased the renal expression of B-Raf and reduced the phosphorylation of extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), and S6. Conclusion: Chronic exercise slows renal cyst growth and damage in PCK rats, despite increasing AVP, with the downregulation of the cAMP/B-Raf/ERK and mTOR/S6 pathways in the kidney of PCK rats.

Exercise training (Ex) has anti-hypertensive and renal protective effects. In this study, we investigate the effects of Ex on mitochondrial fatty acid metabolism in the kidneys of Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS) diet. Eight-week-old, male Dahl-S rats were divided into three groups: (1) normal-salt diet, sedentary (NS-Sed), (2) HS diet, sedentary (HS-Sed), and (3) HS-Ex. The NS and HS groups were fed a diet containing 0.6% and 8% NaCl, respectively. The HS-Ex group performed treadmill running for 8 weeks (5 days/week; 60 min/day at 16–20 m/min, 0% gradient). Renal function and the expression of enzymes and regulators of β-oxidation and electron transport chain (ETC) complexes were assessed. HS increased systolic blood pressure and proteinuria, and Ex ameliorated these defects. HS also reduced creatinine clearance, and Ex ameliorated it. HS reduced the renal expression of enzymes of β-oxidation (carnitine palmitoyltransferase type I (CPTI) and acyl-CoA dehydrogenases (CADs)) and the related transcription factors peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α), and Ex restored this. HS also reduced the renal expression of enzymes in ETC complexes, and Ex restored this expression. Ex ameliorates HS-induced renal damage by upregulating enzymes involved in fatty acid β-oxidation and ETC complexes via increases in PPAR-α and PGC-1α expressions in the kidneys of Dahl-S rats. These results suggest that Ex may have beneficial effects on HS-induced mitochondrial dysfunction in the kidney.