Exercise training contributes to H2O2/VEGF signaling in the lung of rats with monocrotaline-induced pulmonary hypertension

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Colombo, Rafael
Siqueira, Rafaela
Conzatti, Adriana
de Lima Seolin, Bruna Gazzi
Gattelli Fernandes, Tania Regina
Guerra Godoy, Alessandra Eifler
Litvin, Isnard Elman
Silva, Jairo Montemor Augusto [UNIFESP]
Tucci, Paulo José Ferreira [UNIFESP]
da Rosa Araujo, Alex Sander
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Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right ventricle overload. Given that angiogenesis is a key factor involved in the reduction of vascular resistance to blood flow, we tested the hypothesis that aerobic exercise exerts a positive impact on hydrogen peroxide (H2O2) and protein kinase B (Akt) levels in the lung parenchyma. To study the effects of aerobic exercise on lung angiogenesis signaling, Wistar rats were administered monocrotaline (MCT) (60 mg/kg i.p.) or the same volume of saline (0.9% NaCl i.p.). There was an increase in H2O2 (43%) in PAH-trained animals (TM) compared to control animals (SM). H2O2 showed a positive correlation (r = 0.77) with vascular endothelial growth factor (VEGF). VEGF was higher (4.7 fold) in TM animals compared to SM. VEGF and angiopoietin-1 (Ang-1) showed positive staining in the lung parenchyma of TM and SM. Glutathione peroxidase showed higher activity in the TM group (49%) compared to trained control (TC). Aerobic exercise increased the activity of peroxiredoxin (P < 0.05). The increase in VEGF was positively correlated with Akt phosphorylation (r = 0.73). p-Akt was shown to be increased in TM animals when compared to SM animals (2.5 fold). The change in fractional area, fractional shortening and systolic tricuspid annular plane excursion showed improvement after exercise training. Therefore, aerobic exercise promotes H2O2/VEGF/p-Akt signaling for pulmonary physiological angiogenesis. It is associated with an improvement in RV function, as evaluated by echocardiography. (C) 2016 Published by Elsevier Inc.
Vascular Pharmacology. New York, v. 87, p. 49-59, 2016.