Estrogen-dependent depressor response of melatonin via baroreflex afferent function and intensification of PKC-mediated Nav1.9 activation
Estrogen-dependent depressor response of melatonin via baroreflex afferent function and intensification of PKC-mediated Nav1.9 activation
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通过压力反射传入功能和 PKC 介导的 Nav1.9 激活强化来实现褪黑激素的雌激素依赖性抑制反应
DOI：
10.1038/s41401-022-00867-w
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发表时间：
2022-02
影响因子：
8.2
通讯作者：
Bai-Yan Li
中科院分区：
文献类型：
--
作者：
Di Wu;Dan Zhao;Di Huang;Xun Sun;Ke-xin Li;Yan Feng;Qiu-Xin Yan;Xin-yu Li;Chang-Peng Cui;Hu-die Li;Bai-Yan Li
近年来的研究表明，褪黑激素（Melatonin，Mel）通过主动脉压力感受性反射通路在血压调节中起重要作用。在这项研究中，我们研究了压力反射传入通路和梅尔介导的血压调节在生理和高血压条件下大鼠之间的相互作用。将Mel（0.1、0.3和1.0mg/mL）微量注射于大鼠结状神经节（NG）。我们发现，在生理条件下，Mel诱导的雌性大鼠平均动脉压的降低显著大于雄性和去卵巢大鼠。雌性大鼠NG中Mel受体（MTNRs）的表达明显高于雄性大鼠。在L-NAME诱导的高血压和自发性高血压大鼠模型中，MTNR在雄性中上调，但在雌性模型中下调。有趣的是，在雄性高血压模型中发现了Mel诱导的BP降低。在对雌性大鼠已识别的压力感受器神经元（BRN）进行全细胞记录时，我们发现Mel（0.1 μM）通过PKC介导的途径增加Nav1.9电流密度，显着增加了雌性特定的Ah-type BRN亚群的兴奋性。在孤束核的压力感受性神经元中观察到类似的结果，表明AH型神经元的自发和诱发兴奋性突触后电流的易化。本研究揭示了Mel/MTNRs在生理和高血压条件下的雌激素依赖性作用主要是通过Ah-type BRN介导的，这可能为临床上性别特异性的抗高血压治疗提供新的理论依据和策略。
Recent studies suggest that melatonin (Mel) plays an important role in the regulation of blood pressure (BP) via the aortic baroreflex pathway. In this study, we investigated the interaction between the baroreflex afferent pathway and Mel-mediated BP regulation in rats under physiological and hypertensive conditions. Mel (0.1, 0.3, and 1.0 mg/mL) was microinjected into the nodose ganglia (NG) of rats. We showed that Mel-induced reduction of mean arterial pressure in female rats was significantly greater than that in male and in ovariectomized rats under physiological condition. Consistently, the expression of Mel receptors (MTNRs) in the NG of female rats was significantly higher than that of males. In L-NAME-induced hypertensive and spontaneously hypertensive rat models, MTNRs were upregulated in males but downregulated in female models. Interestingly, Mel-induced BP reduction was found in male hypertensive models. In whole-cell recording from identified baroreceptor neurons (BRNs) in female rats, we found that Mel (0.1 μM) significantly increased the excitability of a female-specific subpopulation of Ah-type BRNs by increasing the Nav1.9 current density via a PKC-mediated pathway. Similar results were observed in baroreceptive neurons of the nucleus tractus solitarius, showing the facilitation of spontaneous and evoked excitatory post-synaptic currents in Ah-type neurons. Collectively, this study reveals the estrogen-dependent effect of Mel/MTNRs under physiological and hypertensive conditions is mainly mediated by Ah-type BRNs, which may provide new theoretical basis and strategies for the gender-specific anti-hypertensive treatment in clinical practice.
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影响因子：
5.5
作者：
Sun J;He C;Yan QX;Wang HD;Li KX;Sun X;Feng Y;Zha RR;Cui CP;Xiong X;Gao S;Wang X;Yin RX;Qiao GF;Li BY
通讯作者：
Li BY
影响因子：
10.3
作者：
Y. Zhang;Hua Li;Yichen Pu;S. Gong;Chunfeng Liu;Xinghong Jiang;J. Tao
通讯作者：
Y. Zhang;Hua Li;Yichen Pu;S. Gong;Chunfeng Liu;Xinghong Jiang;J. Tao
影响因子：
7.3
作者：
O. Régrigny;P. Delagrange;E. Scalbert;I. Lartaud‐Idjouadiene;J. Atkinson;J. Chillon
通讯作者：
O. Régrigny;P. Delagrange;E. Scalbert;I. Lartaud‐Idjouadiene;J. Atkinson;J. Chillon
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
E. Grossman;M. Laudon;N. Zisapel
通讯作者：
E. Grossman;M. Laudon;N. Zisapel
影响因子：
4
作者：
Bai, Qian;Shao, Jinping;Dong, Tieli
通讯作者：
Dong, Tieli