Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia

Bibliographic Details
Title: Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia
Authors: Ya-Chen Huang, Zung Fan Yuan, Chang-Huan Yang, Yan-Jhih Shen, Jyun-Yi Lin, Ching Jung Lai
Source: Frontiers in Physiology, Vol 9 (2018)
Publisher Information: Frontiers Media S.A., 2018.
Publication Year: 2018
Collection: LCC:Physiology
Subject Terms: intermittent hypoxia, airway hypersensitivity, lung vagal C fibers, estrogen, lung inflammation, Physiology, QP1-981
More Details: Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-042X
Relation: https://www.frontiersin.org/article/10.3389/fphys.2018.00847/full; https://doaj.org/toc/1664-042X
DOI: 10.3389/fphys.2018.00847
Access URL: https://doaj.org/article/b6de9d6d09434a529df8dd79ddba0f51
Accession Number: edsdoj.b6de9d6d09434a529df8dd79ddba0f51
Database: Directory of Open Access Journals
More Details
ISSN:1664042X
DOI:10.3389/fphys.2018.00847
Published in:Frontiers in Physiology
Language:English