Papel do treinamento físico aeróbio na modulação do balanço pró e antiangiogênico no músculo esquelético de ratos Wistar tratados com dexametasona
Resumen
Dexamethasone (DEX) is widely used in clinic due to its effectiveness as anti-
inflammatory. Nevertheless, its chronic use may cause unwanted metabolic and
hemodynamic alterations, which contribute for the development of hypertension. Arterial
hypertension may be determined by increases in cardiac output or peripheral resistance
and rarefaction may be associated with this response. Microcirculation maintenance is
dependent on the balance between anti-apoptotic and apoptotic proteins and vascular
endothelial growth factor (VEGF), known to be a key-regulator protein of the
physiological angiogenesis, helps to maintain this balance. We recently demonstrated that
high doses with DEX-treatment reduce VEGF protein levels, but the mechanisms
involved in this response were not evaluated. In the other hand, it has been shown that
aerobic training (T) is a good strategy in preventing rarefaction and/or stimulating
angiogenesis, however almost nothing is known about the effects of T on microcirculation
and hypertension induced by DEX. Therefore, the aim of this study was to investigate the
mechanisms induced by T that can contribute to attenuate DEX-induced rarefaction.
Wistar rats were subjected to an aerobic exercise protocol on the treadmill or kept
sedentary for 8 weeks. Additionally, animals were treated with DEX or saline (50μg/kg,
s.c. for 14 days). Groups were: sedentary control (SC), DEX sedentary (SD), trained
control (TC) and trained DEX (TD). Body weight (BW) and arterial pressure (AP) were
analyzed. After euthanasia, adrenal gland, myocardium, SOL and TA muscles were
weighted and normalized by tibia. The cross-sectional area (CSA), capillary:fiber ratio
(C:F ratio), capillary density (CD) and protein levels were evaluated in SOL and TA.
Treatment with DEX caused reduction in BW and in muscle weight (MW) in TA. DEX
treatment also determinated decrease in CSA (TA). Further, C/F and CD were also
reduced (-41 and -43%, SOL) and (-30 and 68.6%, TA). Training was able to prevent C:F
ratio and CD reduction (72.7 and 81.0%) and (32.9 and 54.2%) induced by DEX-
treatment. Furthermore, DEX significantly reduced protein levels in SOL and TA
muscles VEGFR-2 (-14.6% and -20.1%), VEGF (-15.6 and -19%), Bcl-2 (-18.4 and20.5%), Bcl-2/Bax ratio (-29.0 and -13.7%) and p-Bax/Bax (-25.4 and -20%), beyond
COX-2 in TA (-22.8%). DEX also promoted increase in caspase-3 cleaved (25 and 24.1%,
SOL and TA). Moreover, training was able to prevent reduction in proteins levels in
DEX-treated groups in SOL and TA: VEGFR-2 (14.7 and 25.2%), VEGF (15.3 and
25.3%), Bcl-2 (21.6 and 35.5%), Bcl-2/Bax ratio (26.1 and 19.9%), p-Bax/Bax (23.7 and
32.1%) and COX-2 (31.5%) and the increase in caspase-3 cleaved (16.0 and 17.8%). In
conclusion, these results showed that DEX-induced rarefaction promoted imbalance
between apoptotic and angiogenic factors, become one possible causes of hypertension.
However, also showed that aerobic training is a good strategy to attenuate DEX-induced
rarefaction and this response may involve a better balance between apoptotic and
angiogenic factors, which contribute for the attenuation of hypertension.