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Am J Physiol Lung Cell Mol Physiol. 2015 May 1;308(9):L922-30. doi: 10.1152/ajplung.00241.2014. Epub 2015 Mar 6.

Prenatal nicotinic exposure augments cardiorespiratory responses to activation of bronchopulmonary C-fibers.

Author information

1
Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
2
Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico fxu@lrri.org.

Abstract

Rat pups prenatally exposed to nicotine (PNE) present apneic (lethal ventilatory arrest) responses during severe hypoxia. To clarify whether these responses are of central origin, we tested PNE effects on ventilation and diaphragm electromyography (EMGdi) during hypoxia in conscious rat pups. PNE produced apnea (lethal ventilatory arrest) identical to EMGdi silencing during hypoxia, indicating a central origin of this apneic response. We further asked whether PNE would sensitize bronchopulmonary C-fibers (PCFs), a key player in generating central apnea, with increase of the density and transient receptor potential cation channel subfamily V member 1 (TRPV1) expression of C-fibers/neurons in the nodose/jugular (N/J) ganglia and neurotrophic factors in the airways and lungs. We compared 1) ventilatory and pulmonary C-neural responses to right atrial bolus injection of capsaicin (CAP, 0.5 μg/kg), 2) bronchial substance P-immunoreactive (SP-IR) fiber density, 3) gene and protein expressions of TRPV1 in the ganglia, and 4) nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) protein in bronchoalveolar lavage fluid (BALF) and TrkA and TrkB genes in the ganglia between control and PNE pups. PNE markedly strengthened the PCF-mediated apneic response to CAP via increasing pulmonary C-neural sensitivity. PNE also enhanced bronchial SP-IR fiber density and N/J ganglia neural TRPV1 expression associated with increased gene expression of TrkA in the N/G ganglia and decreased NGF and BDNF in BALF. Our results suggest that PNE enhances PCF sensitivity likely through increasing PCF density and TRPV1 expression via upregulation of neural TrkA and downregulation of pulmonary BDNF, which may contribute to the PNE-promoted central apnea (lethal ventilatory arrest) during hypoxia.

KEYWORDS:

cardiorespiratory failure; central apnea; maternal cigarette smoking; sudden infant death syndrome; vagal afferents

PMID:
25747962
PMCID:
PMC4421788
DOI:
10.1152/ajplung.00241.2014
[Indexed for MEDLINE]
Free PMC Article

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