Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure
Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure
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DOI：
10.1161/circulationaha.106.677989
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发表时间：
2007-06-19
期刊：
影响因子：
37.8
通讯作者：
Zucker, Irving H.
中科院分区：
文献类型：
--
作者：
Gao, Lie;Wang, Wei;Zucker, Irving H.
背景 - 在最近的一项研究中，我们证明延髓头端腹外侧氧化应激的增加在慢性心力衰竭（CHF）中观察到的交感神经兴奋中起着关键作用。越来越多的证据表明运动训练对慢性心力衰竭具有抗氧化作用。因此，在本研究中，我们假设长期运动通过中枢抗氧化机制对 CHF 的自主神经活动发挥有益作用。方法和结果 - 在新西兰白兔上进行了实验。所有兔子都用仪器测量平均动脉压、心率和肾交感神经活动并测试压力反射敏感性。运动训练显着降低了基线肾交感神经活动（Max 的 65.8 +/- 5.2% 至 41.3 +/- 3.9% [其中“Max”是直接向兔子外鼻孔喷 50 mL 烟雾诱导的最大肾交感神经活动]，P < 0.05），并增加了心率压力反射曲线的最大增益（2.2 +/- 0.2 至 4.6） CHF 兔子的 +/- 0.7 bpm 每毫米汞柱，P < 0.01）和肾交感神经活动（最大每毫米汞柱的 1.9 +/- 0.2% 至 4.5 +/- 0.4%，P < 0.01）。运动训练增加了 CuZn 超氧化物歧化酶的表达（0.3 +/- 0.1 至 1.5 +/- 0.3 [CuZn 超氧化物歧化酶与微管蛋白的比率]，P < 0.01），并降低了 NAD(P) H 氧化酶亚基 gp91(phox) 蛋白的表达（1.9 +/- 0.2 至 1.2 +/- 0.1 [gp91(phox) 与微管蛋白的比率]。微管蛋白]，P < 0.05）在CHF兔的头端腹外侧延髓中。 CuZn超氧化物歧化酶的中枢过度表达剂量依赖性地降低CHF兔中的基线肾交感神经活性（对照，Max的68.5 +/- 7.1%；1010个腺病毒颗粒，Max的53.2 +/- 4.4%；和1011个腺病毒颗粒，Max的33.7 +/- 3.5%；P < 0.05）。 结论 - 这些结果表明中枢抗氧化机制的上调和中枢促氧化机制的抑制可能有助于运动训练对CHF自主神经活动产生有益的影响。
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.