• Xin Wen, Xue Yu, Rong Huo, Qiu-Xin Yan, Di Wu, Yan Feng, Ying Li, Xun Sun, Xin-Yu Li, Jie Sun, Ke-Xin Li, Qing-Yuan Li, Li-Min Han, Xiao-Long Lu, Yang Liu, Weinian Shou, and Bai-Yan Li.
• Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), Harbin Medical University, Harbin, China.
• Neuroscience. 2019 Jul 15; 411: 150-163.

AbstractSilent angina is a critical phenomenon in the clinic and is more commonly associated with women patients suffering from myocardial ischemia. Its underlying cause remains mysterious in medicine. With our recent discovery of female-specific Ah-type baroreceptor neurons (BRNs), we hypothesize that cardiac analgesia is due to the direct activation of Ah-type BRNs by elevated levels of circulating serotonin (5-HT) myocardial infarction (MI) patients. Electromyography and the tail-flick reflex were assessed in control and MI-model rats to evaluate 5-HT-mediated BP regulation as well as peripheral and cardiac nociception. 5-HT or a 5-HT receptor agonist was microinjected into the nodose ganglion to confirm the involvement of the afferent pathway of the baroreflex arc. An inward current was observed in identified BRNs by applying a whole-cell patch-clamp technique in conjunction with qRT-PCR to verify the afferent-specific action of 5-HT and the expression of 5-HT receptors. Although the tail-flick reflex and mean arterial pressure were dramatically reduced in female MI rats with elevated serum 5-HT, intrapericardial capsaicin-evoked muscular discharges were significantly inhibited in comparing with those of males, which were mimicked by microinjection of 5-HT or SR57227A into the nodose. Ah-type BRNs displayed robust inward currents at lower concentrations of 5-HT than the C-type or the A-type, with significantly increased expression and cellular distribution of 5-HT3AR but not 5-HT3BR compared to the A- and C-types. Activation of 5-HT3AR in Ah-type BRNs by 5-HT contributes significantly to cardiac analgesia, which may suggest the pathogenic condition that silent angina occurs mainly in female patients.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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