No abstract

Overactivity of the intrarenal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. Our group has already demonstrated that aerobic exercise reduces kidney angiotensin II levels and attenuates renal dysfunction under concurrence of diabetes and hypertension. Resistance training (RT) has recently been recognized as a useful therapeutic tool for the treatment chronic diseases and similar to aerobic exercise, has been reported to improve glycemic control. Therefore, the aim of this study was to evaluate the effect of RT on renal function and RAS in diabetic animals, to understand whether this type of exercise is also associated with renoprotection. Wistar rats (3 months old) were randomized into: sedentary control (SC); trained control (TC); sedentary diabetic (SD) and trained diabetic (TD). Animals were made diabetic with a single tail injection of streptozotocin (STZ, 50 mg/Kg). RT was performed on an 110-cm ladder (8 ladder climbs, once/day, 5 days/week, 8 weeks), carrying a load of 50-80% body weight (BW) appended to the tail. At week 8, 24 hr urine volume and albuminuria were evaluated. Kidney was excised and ACE and ACE2 activities were determined (ZPhe-HL and 7-Mca-APK(Dnp), respectively) (Two way ANOVA + Tukey test; P<0.05). RT significantly reduced blood glucose (TD = 449 ± 17 vs. SD = 572 ± 18 mg/dL) and attenuated BW loss of diabetic animals. DM reduced renal ACE activity in sedentary and trained groups (SD = 3.72 ± 0.48, TD = 3.85 ± 0.40 vs. SC = 9.2 ± 0.59 nmol/min/mg), while RT reduced enzyme activity only in control group (TC = 5.14 ± 0.26 vs. SC = 9.2 ± 0.59 nmol/min/mg). RT reduced renal ACE2 in the control group compared to the others (TC = 0.05 ± 0.0001 vs. SC = 0.09 ± 0.004, SD = 0.09 ± 0.003, TD = 0.10 ± 0.002 μM/min/mg), with no effect of diabetes on enzyme activity. RT improved renal function, decreasing urinary volume and albuminuria (DT = 4.13 ± 0.84 vs. SD = 11 ± 2.11 mg/24h) in DT group. The results from the present study show that RT is strongly associated with renoprotection in an experimental model of diabetic nephropathy. Moreover, results show that this improvement on renal function is modulated by other pathways apart from ACE and ACE2 converting enzymes. Financial Support: FAPESP, CAPES, CNPq.

Prior study of our group shown that previous aerobic exercise training improved the damage caused by diabetes mellitus on renal and cardiovascular system. Resistance exercise training, also known as strength training, is traditionally performed to gain muscle mass; however, it is not clear whether this type of exercise modulates renal system. Additionally, it is also unknown whether previous resistance exercise training can potentially influence the kidney and skeletal muscle. Wistar rats were submitted to resistance exercise training in an apparatus developed especially to this type of exercise (8 - 12 climbs/day, 5 days/week, 12 weeks). Previous resistance exercise trained group (PTD) performed for 4 weeks before the establishment of the disease and after this period they were followed by 8 weeks of resistance exercise training. Additional trained groups such as trained diabetic (TD) and trained control (TC) groups were followed by 8 weeks of resistance exercise training. Control groups were also followed (control - C, diabetes - D). We have found that PTD suppressed abnormalities linked to renal system such as, water consumption and amount of urine PTD=71mL vs. DT=127mL vs. D=138mL (measured during metabolic cage period), as well as attenuated proteinuria and kidney weight. Regarding to skeletal muscle, PTD group had increased muscle weight (extensor digitorium longus - EDL; C=192mg, D=116mg, TD=106mg and PTD=126mg; Tibialis anterior, C=780mg, D=496mg, DT=450mg and PTD=535mg); we also found a great muscle force level in the PTD group (C=573g, CT=1037, D=414g, TD=737g and PTD=825g), suggesting a protective effect of previous exercise in this group. PTEN was suppressed in PTD group and Akt and 4EBP1 (upstream and downstream of mTOR) were activated in PTD group, measured by western blot. These data suggest that, resistance exercise performed prior the establishment of the diabetes mellitus can protect kidney from diabetic nephropathy and skeletal muscle from atrophy. The mechanisms by which kidney and skeletal muscle have been improved are linked to mTOR signaling pathway. Further studies will be performed to confirm the potential involvement of this signaling pathway. Support: FAPESP, CAPES, CNPq.