Excess dietary salt alters angiotensinergic regulation of neurons in the rostral ventrolateral medulla.
Excess dietary salt alters angiotensinergic regulation of neurons in the rostral ventrolateral medulla.
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DOI：
10.1161/hypertensionaha.108.118935
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发表时间：
2008-11
期刊：
影响因子：
8.3
通讯作者：
Stocker, Sean D.
中科院分区：
文献类型：
--
作者：
Adams, Julye M.;McCarthy, John J.;Stocker, Sean D.
过量的饮食盐摄入通过在延髓吻侧腹侧（RVLM）激活血管紧张素II (Ang II) 1型受体，增加交感神经活动（SNA）和动脉血压（ABP），从而有助于或加重某些形式的高血压。尽管膳食盐、Ang II和RVLM之间存在相互作用，但没有研究直接研究膳食盐本身是否会改变Ang II依赖性反应和RVLM神经元、SNA和ABP的调节，因此，本研究直接验证了这一假设。雄性Sprague-Dawley大鼠饲喂正常食物，并给予水或0.9% NaCl溶液14 d。在RVLM中单侧注射Ang II(0.6、6和60 pmol)，饮用0.9% NaCl的大鼠的肾SNA和平均ABP显著高于水。然而，饮食盐并没有改变RVLM Ang II型1a受体的mRNA水平，也没有改变SNA和ABP对背外侧肌腱刺激的反应。进一步的实验表明，阻断RVLM Ang II型1受体可显著降低0.9% NaCl（不含水）大鼠肾SNA、内脏SNA和平均ABP。阻断嗜离子性谷氨酸受体无效果。总之，这些发现表明，高盐饮食通过改变RVLM神经元的内在特性，增强了Ang II在RVLM中的交感神经兴奋作用。此外，饮食盐摄入量的增加对外周和大脑RVLM Ang II型1受体的滋补活性有不同的影响，从而调节基线SNA和ABP。
Excess dietary salt intake contributes to or exacerbates some forms of hypertension by increasing sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through angiotensin II (Ang II) type 1 receptor activation in the rostral ventrolateral medulla (RVLM). Despite this interaction among dietary salt, Ang II, and the RVLM, no studies have directly examined whether dietary salt by itself alters Ang II–dependent responses and regulation of RVLM neurons, SNA, and ABP. Therefore, the present study directly tested this hypothesis. Male Sprague-Dawley rats were fed normal chow and given access to water or 0.9% NaCl solution for 14 days. Unilateral injection of Ang II (0.6, 6, and 60 pmol) into the RVLM produced a significantly greater increase in renal SNA and mean ABP of rats drinking 0.9% NaCl versus water. However, dietary salt did not alter mRNA levels of RVLM Ang II type 1a receptors or the SNA and ABP responses to stimulation of the dorsolateral funinculus. Additional experiments demonstrate that blockade of RVLM Ang II type 1 receptors significantly reduced renal SNA, splanchnic SNA, and mean ABP of rats drinking 0.9% NaCl but not water. Blockade of iontotropic glutamate receptors had no effect. Altogether, these findings suggest that elevated dietary salt enhances the sympathoexcitatory actions of Ang II in the RVLM via changes in the intrinsic properties of RVLM neurons. Moreover, elevated dietary salt intake differentially affects the tonic activity of the peripheral versus brain RVLM Ang II type 1 receptors to regulate baseline SNA and ABP.