Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure

Background - In a recent study, we demonstrated that an increase in oxidative stress in the rostral ventrolateral medulla plays a critical role in the sympathoexcitation observed in chronic heart failure ( CHF). Growing evidence indicates that exercise training evokes an antioxidative effect in CHF. In the present study, we therefore hypothesized that long- term exercise exerts its beneficial effect on autonomic activity in CHF via central antioxidative mechanisms. Methods and Results - Experiments were performed on New Zealand White rabbits. All rabbits were instrumented to measure mean arterial pressure, heart rate, and renal sympathetic nerve activity and to test baroreflex sensitivity. Exercise training significantly decreased baseline renal sympathetic nerve activity ( 65.8 +/- 5.2% to 41.3 +/- 3.9% of Max [ where Max is the maximum renal sympathetic nerve activity induced by a 50- mL puff of smoke directed to the external nares of the rabbit], P < 0.05) and increased the maximal gain of the baroreflex curves for heart rate ( 2.2 +/- 0.2 to 4.6 +/- 0.7 bpm per mm Hg, P < 0.01) and renal sympathetic nerve activity ( 1.9 +/- 0.2% to 4.5 +/- 0.4% of Max per mm Hg, P < 0.01) in CHF rabbits. Exercise training increased expression of CuZn superoxide dismutase ( 0.3 +/- 0.1 to 1.5 +/- 0.3 [ ratio of CuZn superoxide dismutase to tubulin], P < 0.01) and decreased NAD( P) H oxidase subunit gp91(phox) protein expression ( 1.9 +/- 0.2 to 1.2 +/- 0.1 [ ratio of gp91(phox) to tubulin], P < 0.05) in the rostral ventrolateral medulla of CHF rabbits. Central overexpression of CuZn superoxide dismutase dose-dependently decreased baseline renal sympathetic nerve activity ( control, 68.5 +/- 7.1% of Max; 1010 particles of adenovirus, 53.2 +/- 4.4% of Max; and 1011 particles of adenovirus, 33.7 +/- 3.5% of Max; P < 0.05) in CHF rabbits. Conclusions - These results suggest that an upregulation in central antioxidative mechanisms and suppressed central prooxidant mechanisms may contribute to the exercise training - induced beneficial effects on autonomic activity in CHF.