ABSTRACT
The effects of exercise training on oxidative stress in gastrocnemius of rats with pulmonary hypertension were studied. Four groups were established: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), trained monocrotaline (TM). Exercise was applied for 4 weeks, 5 days/week, 50-60 min/session, at 60% of VO2 max. Right ventricular (RV) pressures were measured, heart and gastrocnemius were removed for morphometric/biochemical analysis. Lipid peroxidation (LPO), H2O2, GSH/GSSG, and activity/expression of antioxidant enzymes were evaluated. Increased RV hypertrophy, systolic and end-diastolic pressures (RVEDP) were observed in SM animals, and the RVEDP was decreased in TM vs. SM. H2O2, SOD-1, and LPO were higher in the SM group than in SC. In TM, H2O2 was further increased when compared to SM, with a rise in antioxidant defences and a decrease in LPO. GSH/GSSG was higher only in the TC group. Exercise induced an efficient antioxidant adaptation, preventing oxidative damage to lipids.
Subject(s)
Monocrotaline , Pulmonary Arterial Hypertension , Animals , Antioxidants/metabolism , Glutathione Disulfide/metabolism , Hydrogen Peroxide/metabolism , Lipids , Monocrotaline/metabolism , Monocrotaline/toxicity , Muscle, Skeletal , Oxidative Stress , Rats , Rats, WistarABSTRACT
Pulmonary arterial hypertension (PAH) is a disease that increases the pulmonary vascular resistance, causing hypertrophy and subsequent right heart failure. Oxidative stress is involved in the pathogenesis of PAH, and estrogen is considered an antioxidant. Thus, the aim of this study was to test the hypothesis that estrogen could attenuate PAH by modulating oxidative stress. Female Wistar rats were ovariectomized or suffered the surgery simulation (sham). After 7 days, subcutaneous pellets with 17ß-estradiol or sunflower oil were implanted. At this time, PAH was induced by means of a single dose of monocrotaline (MCT) (60 mg·kg(-1) i.p.). The experimental groups were as follows: (1) sham, (2) sham + MCT, (3) ovariectomy (O), (4) ovariectomy + MCT (OM), (5) ovariectomy + estrogen replacement + MCT (ORM). Hemodynamic measurements were performed 21 days after MCT or saline. Nonovariectomized animals were assessed in the stage of diestrus. Afterwards, the rats were killed to collect the heart, the lung and the liver to evaluate morphometry. Samples of the right ventricle were used to analyse the reduced glutathione : oxidized glutathione ratio. Lung congestion in the OM group, which was decreased in the ORM group, was observed. Right ventricle end-diastolic pressure was increased in the OM and the ORM groups. The glutathione ratio decreased in the groups O, OM and ORM. The data suggest that estrogen can exert great influence on the cellular redox balance. The maintenance of physiological estrogen levels may help to avoid the appearance of pulmonary oedema, characteristic of this model of PAH, and right ventricular failure.
