Larson Robert A, Gui Le, Huber Michael J, Chapp Andrew D, Zhu Jianhua, LaGrange Lila P, Shan Zhiying, Chen Qing-Hui
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; and.
Am J Physiol Heart Circ Physiol. 2015 Jun 15;308(12):H1547-55. doi: 10.1152/ajpheart.00832.2014. Epub 2015 Apr 10.
Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to PVN-injected apamin compared with NS control rats. Next, we sought to examine the individual contributions of HS and subcutaneous infusion of ANG II on PVN SK channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats with HS alone were significantly attenuated compared with NS-fed rats. In contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II-treated rats were slightly attenuated with SSNA, demonstrating no statistical difference compared with NS-fed rats, whereas MAP responses to PVN-injected apamin were similar to NS-fed rats. Finally, Western blot analysis showed no statistical difference in SK1-SK3 expression in the PVN between NS and ANG II-salt HTN. We conclude that reduced SK channel function in the PVN is involved in the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a dominant role in reducing SK channel function, thus contributing to sympathoexcitation in ANG II-salt HTN.
皮下注射血管紧张素II（ANG II）和高盐饮食（HS）导致的高血压（HTN）涉及交感神经兴奋。最近，我们报道了在ANG II - 盐性高血压中，小电导钙激活钾（SK）电流降低，室旁核（PVN）中交感神经节前神经元的兴奋性增加。在此，我们假设ANG II - 盐性高血压会伴有PVN中SK通道活性的改变，这可能在体内导致交感神经兴奋。在正常盐（NS）摄入的麻醉大鼠中，双侧PVN微量注射SK通道阻滞剂蜂毒素（各12.5 pmol/50 nl）可显著提高内脏交感神经活动（SSNA）、肾交感神经活动（RSNA）和平均动脉压（MAP）。相比之下，与NS对照大鼠相比，ANG II - 盐性高血压大鼠对PVN注射蜂毒素的SSNA、RSNA和MAP反应明显减弱（P < 0.05）。接下来，我们试图研究HS和皮下注射ANG II对PVN中SK通道功能的各自作用。与NS喂养的大鼠相比，仅HS喂养的大鼠对PVN注射蜂毒素的SSNA、RSNA和MAP反应明显减弱。相比之下，ANG II处理的大鼠对PVN注射蜂毒素的交感神经活动反应中，SSNA略有减弱，与NS喂养的大鼠相比无统计学差异，而对PVN注射蜂毒素的MAP反应与NS喂养的大鼠相似。最后，蛋白质免疫印迹分析显示，NS组和ANG II - 盐性高血压组PVN中SK1 - SK3的表达无统计学差异。我们得出结论，PVN中SK通道功能降低与ANG II - 盐性高血压相关的交感神经兴奋有关。高盐饮食可能在降低SK通道功能中起主要作用，从而导致ANG II - 盐性高血压中的交感神经兴奋。
