Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Japan.
Hypertens Res. 2013 Jun;36(6):504-12. doi: 10.1038/hr.2012.224. Epub 2013 Jan 31.
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.
醛固酮和盐皮质激素受体 (MR) 阻滞剂对延髓头端腹外侧区 (RVLM) 节前神经元的影响已有深入研究。为了直接研究醛固酮、依普利酮（一种 MR 阻滞剂）、FAD286（一种醛固酮合酶抑制剂）和苯并咪（一种上皮钠通道 (ENaC) 阻滞剂）是否影响 RVLM 神经元，我们使用全细胞膜片钳技术，在脑-脊髓灌流液中加入这些药物后，检测 RVLM 神经元的膜电位 (MP) 变化。醛固酮灌流 (0.1 μmol/l) 使 RVLM 神经元去极化。相比之下，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，进行了 FAD286 灌流 (10 μmol/l)，FAD 灌流期间 RVLM 神经元超极化。这些数据表明，MR 存在，并且醛固酮在脑干中合成。苯并咪灌流 (1 μmol/l) 使 RVLM 神经元超极化。为了阐明醛固酮、依普利酮、FAD286 和苯并咪是否直接作用于 RVLM 神经元，我们使用低钙高镁溶液阻断 RVLM 神经元的突触输入，在低钙灌流期间加入上述药物。醛固酮灌流期间，RVLM 神经元去极化，依普利酮、FAD286 或苯并咪灌流期间超极化。重要的是，当苯并咪溶液灌流后加入醛固酮时，RVLM 神经元的 MPs 没有去极化。这些结果表明，MR 存在于 RVLM 神经元中，醛固酮在 RVLM 中合成。RVLM 神经元本身具有 ENaC，醛固酮通过 ENaC 激活 RVLM 神经元。
