Efeitos do treinamento físico na hipertensão e na atrofia muscular em ratos tratados com dexametasona

Abstract

Dexamethasone (DEX) is widely used due to its potent anti-inflammatory effect, although its chronic use may cause unwanted effects, including arterial hypertension (H) and muscle atrophy. The mechanisms responsible for these effects remain unclear. Nervous system, microcirculation and oxidative stress may be involved in H. In addition, oxidative stress may also be responsible for muscle atrophy. On the other hand, exercise training (T) its recommended for H treatment and it is an oxidative stress modulator. The aim of this study was to investigate if DEX-induced H is associated with changes in the autonomic nervous system, microcirculation and oxidative stress. Moreover, it evaluated if arterial pressure (AP) reduction induced by T is associated with a better balance of these mechanisms. Still, it investigated if muscle atrophy was also involved with oxidative stress and if T could improve this response. Rats were submitted to T for 8 weeks or kept sedentary and then treated or not with DEX (50μg/kg/day for 14 days), composing four groups: sedentary control (SC), sedentary DEX (SD), trained control (TC) and trained DEX (TD). Body weight (BW), basal AP, autonomic balance to the heart and sympathetic nerve activity to the vessels were analyzed. Aorta was collected for evaluation of oxidative stress and tibialis anterior (TA) and soleus (SOL) muscles were collected for microcirculation histological analysis and for gene and protein evaluations of gp91phox, p47phox, SOD-1, SOD-2 and CAT. DEX decreased BW (-29.1g), increased AP (+12.1%), TA muscle atrophy (- 8.2%), increased low-frequency waves to the heart (+58.5%) and vessels (+96.6%), decreased high-frequency waves to the heart (-12.0%), reduced capillary density and capillary-fiber-ratio (C:F ratio) in TA (respectively -21.9%, -11.1%) and SOL (respectively -25.9%, -22.2%) muscles. In contrast, T mitigated AP increase (-10.0%), atennuated low-frequency waves increase to the heart (-21.5%) and vessels (-8.4%) and also high-frequency waves decrease to the heart (+8.4%). Moreover, T prevented capillary density and C:F ratio reductions in TA (respectively, +46.0% +31.6%) and SOL (respectively, +44.4% +37.5%) muscles and increased SOD-2 and CAT protein level in TA (respectively + 37.4%, + 20.9%) and SOL (respectively +15.4%, +18.0%) muscles. The results allow us to suggest that DEX-induced H may be associated with changes in sympathetic nervous system to the heart and vessels, parasympathetic nervous system to the heart and also microcirculation rarefaction. In the other hand, T was able to mitigate AP increase due to autonomic balance improvement and rarefaction prevention. Since T increased rat´s antioxidant capacity independent of attenuation of muscle atrophy, we may suggest that oxidative stress is not involved in DEX-induced muscle atrophy.