Impacto do treinamento físico combinado no desenvolvimento das disfunções cardiovasculares e neuroimunes induzidas pela sobrecarga de frutose em ratos hipertensos

Abstract

The aim of the present study was to evaluate the impact of combined exercise training on the development of cardiovascular and neuroimmune dysfunctions induced by fructose overload in sedentary hypertensive (SH), SHR + fructose (HF) and SHR + fructose + training (Treadmill + ladder, 60 days, 40-60% of maximal capacity) (HFTC). The groups were divided into subgroups evaluated at 7, 15, 30 and 60 days (n=6/group/time). Fructose was offered in drinking water (10%). Metabolic, hemodynamic, autonomic, inflammatory, and oxidative stress parameters were evaluated. Regarding the metabolic profile, the HF group showed increase in white adipose tissue in relation to the H group and the HFTC group diminished these values values at 60 days (HF: 1.91± 0.10 vs. H: 1.61±0.11 and HFTC: 1.42±0.13 g). The HF group presented reduction in insulin sensitivity (HF: 3.15±0.2 vs. H: 3.96±0,1 and HFTC: 4.32±0.2 %/min) at 60 days in relation to H and HFTC groups. The HF group increased triglycerides (TG) when compared to H group at 60 days of protocol (HF:139±7 vs. H: 106±5 and HFTC:107±8 mg/dL). TG were lower in the HFTC group than in the HF group at 60 days. Fructose consumption (HF) induced a further increase in mean arterial pressure (MAP) at 30 and 60 days in SHR (HF-30 days: 1534 e HF-60 days: 184±4 vs. H-30 days: 1413 e H-60 days: 1653 mmHg). On the other hand, combined exercise training reduced MAP in 30 and 60 days of fructose overload in relation to the HF group (HFTC: 142±8 and 167±6 mmHg). There was a decrease on heart rate variability (VAR-PI) in 7 days and 60 days in the HF group (10.5±1.3 and 40.81± 6.12 ms2) in relation to the H group (23±1.5 and 59.7 ±3.4 ms2); the HFTC group did not presented this impairment (26.8±2.1 and 70.4±5.9 ms2). In addition, the HF group had a lower alpha index (spontaneous baroreflex) at 7 days compared to the H group (0.23±0.03 vs. 0.35±0.01 ms/mmHg), which was not observed in the HFTC group. There was an increase in IL-6 and TNFα in cardiac tissue at 15, 30 and 60 days in the HF and HFTC groups compared to the H groups. The HFTC group presented higher IL-10 values in the heart at 7 days compared to the HF group (28±1 vs. 16±1 pg/mg of protein). The HF group presented increase in cardiac lipoperoxidation at 30 and 60 days in relation to the H group. The HFTC group decreased lipoperoxidation compared to HF group at 60 days (1302±58 vs. 1956±215 cps/mg protein) and there was also reduction in protein oxidation in this time. In addition, there was an increase in NADPH oxidase in the HF group at 60 days when compared to the H group and reduction in this parameter in the HFTC group in relation to the HF group at the same time (H: 0.18±0.02; HF: 0.46 ±0.04; HFTC 0.35 ±0.03 μm/mg protein). Considering the redox balance, the HFTC group presented increase in this evaluation in 7, 15, 30 and 60 days in relation to H and HF groups. Our results show that only 7 days of fructose consumption impaired the autonomic control of the circulation, followed by reduction in plasma nitrites and increase in cardiac IL-6 and TNF- in 15 days, culminating in increased cardiac protein and lipids damage, which are probably associated with the appearance of cardiometabolic dysfunctions after 30 days of protocol in SHR. In addition, combined exercise training prevented the development of autonomic dysfunction in this model, which probably promoted favorable neuroimmune changes and oxidative stress profile, culminating in a marked attenuation of cardiometabolic dysfunctions in SHR submitted to fructose consumption. Together our findings reinforce the role of the autonomic nervous system in the genesis of cardiometabolic dysfunctions and evidence an important role of combined exercise training in the prevention of these alterations.