Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM
Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM
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DOI：
10.1038/hr.2012.224
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发表时间：
2013-06
影响因子：
5.4
通讯作者：
Naoki Oshima;H. Onimaru;Hanako Takechi;Kojiro Yamamoto;Atsushi Watanabe;Takahiro Uchida;Y. Nishida;T. Oda;H. Kumagai
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文献类型：
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作者：
Naoki Oshima;H. Onimaru;Hanako Takechi;Kojiro Yamamoto;Atsushi Watanabe;Takahiro Uchida;Y. Nishida;T. Oda;H. Kumagai
醛固酮和盐皮质激素受体（MR）阻断剂对延髓头端腹外侧区（RVLM）前交感神经元的作用已被充分研究。直接调查是否醛固酮，依普利酮（MR阻滞剂），FAD 286（醛固酮合成酶抑制剂）和苯扎米尔（上皮钠通道（ENaC）阻滞剂）影响RVLM神经元，我们研究了在球脊髓RVLM神经元的膜电位（MP）的变化，使用全细胞膜片钳技术在与这些药物的脑干脊髓制剂灌注。醛固酮灌流（0.1 μmol/l）使RVLM神经元去极化。相反，依普利酮灌流（1 μmol/l）使它们超极化。为了评估醛固酮的存在，进行FAD 286灌流（10 μmol/l），在FAD灌流期间，RVLM神经元变得超极化。这些数据表明，MR的存在和醛固酮是在脑干合成。苯扎米尔灌流（1 μmol/l）使RVLM神经元超极化。为明确醛固酮、依普利酮、FAD 286和苯扎明是否直接作用于RVLM神经元，用低钙高镁溶液阻断RVLM神经元的突触输入，并在低钙灌流过程中加入上述药物。在醛固酮灌流期间，RVLM神经元变得去极化，而在依普利酮、FAD 286或苯扎明灌流期间，它们变得超极化。重要的是，当苯扎米尔溶液后灌流醛固酮时，RVLM神经元的MP并没有去活化。这些结果表明，MR存在于RVLM神经元和醛固酮合成的RVLM。RVLM神经元本身具有ENaCs，并且ENaCs是醛固酮激活RVLM神经元的潜在机制。
The effects of aldosterone and mineralocorticoid receptor (MR) blockers on presympathetic neurons in the rostral ventrolateral medulla (RVLM) are well studied. To directly investigate whether aldosterone, eplerenone (an MR blocker), FAD286 (an aldosterone synthase inhibitor) and benzamil (an epithelial sodium channel (ENaC) blocker) affect RVLM neurons, we examined changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion with these drugs to brainstem–spinal cord preparations. Aldosterone superfusion (0.1 μmol/l) depolarized the RVLM neurons. In contrast, eplerenone superfusion (1 μmol/l) hyperpolarized them. To evaluate the existence of aldosterone, FAD286 superfusion (10 μmol/l) was performed, and the RVLM neurons became hyperpolarized during FAD superfusion. These data suggest that MRs exist and that aldosterone is synthesized in the brainstem. Benzamil superfusion (1 μmol/l) hyperpolarized the RVLM neurons. To clarify whether aldosterone, eplerenone, FAD286 and benzamil acted directly on the RVLM neurons, a low-Ca 2+, high-Mg 2+ solution was used to block the synaptic input to the RVLM neurons, and the above-mentioned drugs were added during the low-Ca 2+ superfusion. During the aldosterone superfusion, the RVLM neurons became depolarized, and they became hyperpolarized during eplerenone, FAD286 or benzamil superfusion. Importantly, when aldosterone was superfused after the benzamil solution, the MPs of the RVLM neurons did not depolarize. These results suggest that MRs are present in the RVLM neurons and that aldosterone is synthesized in the RVLM. The RVLM neurons themselves possess ENaCs, and ENaCs are the underlying mechanism by which aldosterone activates RVLM neurons.