Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline.

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg-1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor ß (ER-ß). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.

Aerobic Exercise Promotes a Decrease in Right Ventricle Apoptotic Proteins in Experimental Cor Pulmonale.

Pulmonary arterial hypertension is characterized by progressive increases in resistance and pressure in the pulmonary artery and Cor pulmonale. The effect of exercise on hydrogen peroxide-dependent signaling in the right ventricle (RV) of Cor pulmonale rats was analyzed. Rats were divided into sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM) groups. Rats underwent exercise training (60% of VO2 max) for 5 weeks, with 3 weeks after monocrotaline injection (60 mg/kg intraperitoneally). Pulmonary resistance was enhanced in SM (2.0-fold) compared with SC. Pulmonary artery pressure was increased in SM (2.7-fold) and TM (2.6-fold) compared with their respective controls (SC and TC). RV hypertrophy indexes increased in SM compared with SC. Hydrogen peroxide was higher in SM (1.7-fold) than SC and was reduced by 47% in TM compared with SM. p-Akt was increased in TM (2.98-fold) compared with SM. The Bax/Bcl-2 ratio and caspase 3 were also increased (2.9-fold and 3.9-fold, respectively) in SM compared with SC. Caspase 3 was decreased in TM compared with SM (P < 0.05). Therefore, exercise training promoted a beneficial response by decreasing hydrogen peroxide concentrations, and consequently, apoptotic signaling in RV.