Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension?
Does enhanced respiratory-sympathetic coupling contribute to peripheral neural mechanisms of angiotensin II-salt hypertension?
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增强的呼吸交感神经耦合是否有助于血管紧张素 II 盐高血压的周围神经机制？
DOI：
10.1113/expphysiol.2009.047399
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发表时间：
2010
影响因子：
2.7
通讯作者：
Osborn,JohnW
中科院分区：
文献类型：
--
作者：
Toney,GlennM;Pedrino,GustavoR;Fink,GregoryD;Osborn,JohnW
在实验动物中由血管紧张素II（Ang II）的慢性输注引起的高血压可能至少部分地通过持续的交感神经活动（SNA）的升高来介导。然而，SNA相对于非神经机制在介导Ang II诱导的高血压中的贡献是一个激烈争论的领域，并且仍然没有解决。我们推测血管紧张素II的交感兴奋作用与膳食盐摄入水平直接相关。为了验证这一假设，将慢性仪器大鼠置于0.1（低），0.4（正常）或2.0%NaCl饮食（高），并在对照期后，给予Ang II（150 ng kg-1 min-1，s.c.）10-14天。在高盐饮食的大鼠中，对Ang II的高血压反应最大（Ang II-盐高血压），这与通过去甲肾上腺素溢出和神经节阻滞测量的“全身”交感神经活性增加有关。器官特异性SNA的间接和直接测量结果显示，Ang II盐大鼠中存在明显的“交感神经特征”，其特征为内脏血管床SNA增加，肾脏SNA短暂减少，后肢SNA无变化。电生理学实验表明，增加交感神经流出在血管紧张素II盐大鼠是不可能涉及激活延髓头端腹外侧（RVLM）血管神经元与压力敏感性心脏节律性放电。相反，另一组RVLM神经元，在离散的突发放电夸大了自发活动与血管紧张素II盐高血压大鼠。虽然它们的放电在静息动脉压水平下不是心脏节律性的，但它似乎是压力敏感的。因此，这些爆发放电的RVLM神经元可能具有血管扩张功能，这与它们向脊髓的轴突投射一致。这些神经元的爆发性放电是呼吸节律的，并由呼吸网络驱动。鉴于内脏SNA强烈耦合到呼吸，我们假设，增强中央交感神经-血管紧张素神经元耦合的RVLM可能是一个重要的机制，有助于夸大内脏交感神经流出的血管紧张素II盐高血压。这一假设仍有待于在今后的调查中直接加以检验。
Hypertension caused by chronic infusion of angiotensin II (Ang II) in experimental animals is likely to be mediated, at least in part, by an elevation of ongoing sympathetic nerve activity (SNA). However, the contribution of SNA relative to non‐neural mechanisms in mediating Ang II‐induced hypertension is an area of intense debate and remains unresolved. We hypothesize that sympathoexcitatory actions of Ang II are directly related to the level of dietary salt intake. To test this hypothesis, chronically instrumented rats were placed on a 0.1 (low), 0.4 (normal) or 2.0% NaCl diet (high) and, following a control period, administered Ang II (150 ng kg−1min−1,s.c.) for 10–14 days. The hypertensive response to Ang II was greatest in rats on the high‐salt diet (Ang II–salt hypertension), which was associated with increased ‘whole body’ sympathetic activity as measured by noradrenaline spillover and ganglionic blockade. Indirect and direct measures of organ‐specific SNA revealed a distinct ‘sympathetic signature’ in Ang II–salt rats characterized by increased SNA to the splanchnic vascular bed, transiently reduced renal SNA and no change in SNA to the hindlimbs. Electrophysiological experiments indicate that increased sympathetic outflow in Ang II–salt rats is unlikely to involve activation of rostral ventrolateral medulla (RVLM) vasomotor neurons with barosensitive cardiac rhythmic discharge. Instead, another set of RVLM neurons that discharge in discrete bursts have exaggerated spontaneous activity in rats with Ang II–salt hypertension. Although their discharge is not cardiac rhythmic at resting levels of arterial pressure, it nevertheless appears to be barosensitive. Therefore, these burst‐firing RVLM neurons presumably serve a vasomotor function, consistent with their having axonal projections to the spinal cord. Bursting discharge of these neurons is respiratory rhythmic and driven by the respiratory network. Given that splanchnic SNA is strongly coupled to respiration, we hypothesize that enhanced central respiratory–vasomotor neuron coupling in the RVLM could be an important mechanism that contributes to exaggerated splanchnic sympathetic outflow in Ang II–salt hypertension. This hypothesis remains to be tested directly in future investigations.