Exercise training decreases oxidative stress in skeletal muscle of rats with pulmonary arterial hypertension.

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.

Enhanced beta-adrenergic response in rat papillary muscle by inhibition of inducible nitric oxide synthase after myocardial infarction.

AIM: Myocardial infarction (MI) induces a progressive ventricular remodelling leading to a contractility depression. During the acute phase of MI inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production increases in the heart. The aim of this study was to investigate the role of iNOS in the left ventricular contractility at 3 days after MI. METHODS: Wistar rats were divided into: sham operated (SHAM, n = 23), infarction (INF, n = 18); sham operated plus the iNOS inhibitor, S-methylisothiourea (SMT) 5 mg kg(-1) day(-1), i.p. treatment (SHAM-SMT, n = 26) and infarction plus SMT (INF-SMT, n = 22). Concentration-response curves for isoprenaline, Ca(2+) and frequency-force curve were studied in isolated papillary muscle from left ventricle. RESULTS: After 3 days infarct area was similar between groups. SMT treatment reduced the time to peak tension during frequency-force curve in the infarct group (SHAM = 63 +/- 3; SHAM-SMT = 71 +/- 3; INF = 90 +/- 4; INF-SMT = 79 +/- 4 ms, P < 0.05) and increased the maximal response to isoprenaline (SHAM = 0.93 +/- 0.11; SHAM-SMT = 1.13 +/- 0.1; INF =0.84 +/- 0.16; INF-SMT = 1.49 +/- 0.15 g mm(-2), P < 0.05). The response to Ca(2+) was equally reduced in the INF and INF-SMT groups. SMT treatment did not change the reduced post-rest potentiation performed by INF group, but attenuated the plasma nitrite and nitrate (NOx) levels in the INF group without any haemodynamic effect. CONCLUSION: These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the beta-adrenergic inotropic responses.