John D. Dingell Veterans Affairs Medical Center, Departments of Internal Medicine and Physiology, Wayne State University School of Medicine, Detroit, Michigan.
Am J Physiol Regul Integr Comp Physiol. 2013 Dec;305(11):R1390-400. doi: 10.1152/ajpregu.00546.2012. Epub 2013 Oct 2.
Exercise-induced changes in γ-aminobutyric acid (GABA) or nitric oxide signaling within the paraventricular nucleus (PVN) have not been studied in renovascular hypertension. We tested whether exercise training decreases mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in two-kidney, one-clip (2K-1C) hypertensive rats due to enhanced nitric oxide or GABA signaling within PVN. Conscious, unrestrained male Sprague-Dawley rats with either sham (Sham) or right renal artery clipping (2K-1C) were assigned to sedentary (SED) or voluntary wheel running (ExT) for 6 or 12 wk. MAP and angiotensin II (ANG II) were elevated in 2K-1C SED rats. The 2K-1C ExT rats displayed lower MAP at 6 wk that did not decline further by 12 wk. Plasma ANG II was lower in 2K-1C ExT rats. Increases in MAP, heart rate, and RSNA to blockade of PVN nitric oxide in 2K-1C SED rats were attenuated compared with either Sham group. Exercise training restored the responses in 2K-1C ExT rats. The increase in MAP in response to bicuculline was inversely correlated with baseline MAP. The rise in MAP was lower in 2K-1C SED vs. either Sham group and was normalized in the 2K-1C ExT rats. Paradoxically, heart rate and RSNA responses were not diminished in 2K-1C SED rats but were significantly lower in the 2K-1C ExT rats. Thus the decrease in arterial pressure in 2K-1C hypertension associated with exercise training is likely due to diminished excitatory inputs to PVN because of lower ANG II and higher nitritergic tone rather than enhanced GABA inhibition of sympathetic output.
在肾血管性高血压中，尚未研究过室旁核（PVN）内γ-氨基丁酸（GABA）或一氧化氮信号的运动诱导变化。我们测试了运动训练是否会由于 PVN 内一氧化氮或 GABA 信号增强而降低两肾一夹（2K-1C）高血压大鼠的平均动脉压（MAP）和肾交感神经活动（RSNA）。有假手术（Sham）或右肾动脉夹闭（2K-1C）的清醒、不受约束的雄性 Sprague-Dawley 大鼠被分配到久坐（SED）或自愿轮跑（ExT）6 或 12 周。2K-1C SED 大鼠的 MAP 和血管紧张素 II（ANG II）升高。2K-1C ExT 大鼠在 6 周时显示出较低的 MAP，但到 12 周时并未进一步下降。2K-1C ExT 大鼠的血浆 ANG II 较低。与 Sham 组相比，2K-1C SED 大鼠 PVN 一氧化氮阻断时 MAP、心率和 RSNA 的增加减弱。运动训练使 2K-1C ExT 大鼠的反应得到恢复。MAP 对荷包牡丹碱的反应增加与基线 MAP 呈反比。2K-1C SED 大鼠的 MAP 升高幅度低于任何 Sham 组，在 2K-1C ExT 大鼠中得到正常化。矛盾的是，2K-1C SED 大鼠的心率和 RSNA 反应没有减弱，但在 2K-1C ExT 大鼠中明显降低。因此，与运动训练相关的 2K-1C 高血压中动脉压的降低可能是由于 ANG II 降低和硝化神经递质张力增加而不是 GABA 抑制交感神经输出增强导致 PVN 兴奋性传入减少所致。
