Serotonin-Mediated Cardiac Analgesia via Ah-Type Baroreceptor Activation Contributes to Silent Angina and Asymptomatic Infarction

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, Bai Yan Li

Research output: Contribution to journalArticle

Abstract

Silent 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.

Original languageEnglish (US)
Pages (from-to)150-163
Number of pages14
JournalNeuroscience
Volume411
DOIs
StatePublished - Jul 15 2019

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Keywords

  • Baroreflex
  • blood pressure
  • electromyography (EMG)
  • myocardial infarction (MI)
  • serotonin (5-hydroxytryptamine, 5-HT)
  • silent angina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wen, X., Yu, X., Huo, R., Yan, Q. X., Wu, D., Feng, Y., Li, Y., Sun, X., Li, X. Y., Sun, J., Li, K. X., Li, Q. Y., Han, L. M., Lu, X. L., Liu, Y., Shou, W., & Li, B. Y. (2019). Serotonin-Mediated Cardiac Analgesia via Ah-Type Baroreceptor Activation Contributes to Silent Angina and Asymptomatic Infarction. Neuroscience, 411, 150-163. https://doi.org/10.1016/j.neuroscience.2019.05.045