Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation
Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation
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DOI：
10.1113/jphysiol.2013.257204
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发表时间：
2013-09-01
影响因子：
5.5
通讯作者：
Brailoiu, Eugen
中科院分区：
文献类型：
--
作者：
Brailoiu, G. Cristina;Benamar, Khalid;Brailoiu, Eugen
除了作用于盐皮质激素受体外，最近还显示醛固酮激活血管细胞中的G蛋白偶联雌激素受体（GPER）。鉴于GPER在迷走神经心脏控制中的新作用，我们研究了醛固酮是否激活大鼠疑核中的GPER。醛固酮产生了剂量依赖性的增加，在逆行标记的心脏迷走神经元疑核的胞质Ca 2+浓度，反应被废除的GPER拮抗剂G-36预处理，但不受盐皮质激素受体拮抗剂，螺内酯和依普利酮。在无钙生理盐水中，对醛固酮的反应对阻断溶酶体的钙释放不敏感，而通过阻断Ryanodine受体的钙释放可降低醛固酮的反应，并通过阻断IP 3受体消除醛固酮的反应。醛固酮可通过P/Q型钙通道诱导钙内流，而不通过L型和N型钙通道。醛固酮可引起疑核迷走神经元的去极化，而疑核迷走神经元对GPER的拮抗作用敏感，对盐皮质激素受体的拮抗作用不敏感。使用遥测心率的体内研究表明，向疑核中微量注射醛固酮在清醒的自由活动的大鼠中产生剂量依赖性心动过缓。醛固酮诱导的心动过缓被GPER拮抗剂阻断，但不能被盐皮质激素受体拮抗剂阻断。总之，我们首次报道醛固酮通过激活疑核的心脏迷走神经元GPER降低心率。
In addition to acting on mineralocorticoid receptors, aldosterone has been recently shown to activate the G protein-coupled oestrogen receptor (GPER) in vascular cells. In light of the newly identified role for GPER in vagal cardiac control, we examined whether or not aldosterone activates GPER in rat nucleus ambiguus. Aldosterone produced a dose-dependent increase in cytosolic Ca2+ concentration in retrogradely labelled cardiac vagal neurons of nucleus ambiguus; the response was abolished by pretreatment with the GPER antagonist G-36, but was not affected by the mineralocorticoid receptor antagonists, spironolactone and eplerenone. In Ca2+-free saline, the response to aldosterone was insensitive to blockade of the Ca2+ release from lysosomes, while it was reduced by blocking the Ca2+ release via ryanodine receptors and abolished by blocking the IP3 receptors. Aldosterone induced Ca2+ influx via P/Q-type Ca2+ channels, but not via L-type and N-type Ca2+ channels. Aldosterone induced depolarization of cardiac vagal neurons of nucleus ambiguus that was sensitive to antagonism of GPER but not of mineralocorticoid receptor. in vivo studies, using telemetric measurement of heart rate, indicate that microinjection of aldosterone into the nucleus ambiguus produced a dose-dependent bradycardia in conscious, freely moving rats. Aldosterone-induced bradycardia was blocked by the GPER antagonist, but not by the mineralocorticoid receptor antagonists. In summary, we report for the first time that aldosterone decreases heart rate by activating GPER in cardiac vagal neurons of nucleus ambiguus.