Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus
Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus
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DOI：
10.1152/ajpheart.00832.2014
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发表时间：
2015-06-15
影响因子：
4.8
通讯作者：
Chen, Qing-Hui
中科院分区：
文献类型：
--
作者：
Larson, Robert A.;Gui, Le;Chen, Qing-Hui
皮下输注ANG II和饮食高盐（HS）摄入导致的高血压（HTN）涉及交感神经兴奋。最近，我们报道减少小电导钙激活的K+（SK）电流和增加的室旁核（PVN）的前交感神经元的兴奋性ANG II盐HTN。在这里，我们假设ANG II盐HTN将伴随着改变PVN SK通道活性，这可能有助于体内交感神经兴奋。在正常盐（NS）摄入的麻醉大鼠，双侧PVN微量注射SK通道阻断剂apamin（12.5pmol/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）。与此相反，ANG II盐HTN大鼠对PVN注射的apamin的SSNA、RSNA和MAP反应与NS对照组相比显著减弱（P < 0.05）。接下来，我们试图检查HS和皮下输注ANG II对PVN SK通道功能的个体贡献。SSNA，RSNA，和MAP反应PVN注射apamin在大鼠HS单独与NS喂养的大鼠相比，显着减弱。与此相反，交感神经活动反应PVN注射apamin在ANG II治疗的大鼠略有衰减与SSNA，证明没有统计学差异相比，NS喂养的大鼠，而MAP反应PVN注射apamin是相似的NS喂养的大鼠。最后，Western印迹分析显示NS和ANG II盐HTN之间PVN中SK 1-SK 3表达无统计学差异。我们的结论是减少SK通道功能的PVN参与了交感神经兴奋与ANG II盐HTN。饮食HS可能在降低SK通道功能中起主导作用，从而有助于ANG II盐HTN的交感神经兴奋。
Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca2+-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.