Prenatal nicotinic exposure increases pulmonary C neural response to capsaicin associated with upregulation of TRPV1 in nodose ganglia neurons (713.4)

Abstract

We have reported that stimulation of pulmonary C‐fibers (PCFs) during hypoxia produces a long‐lasting apnea or lethal ventilatory arrest in rats and that PNE promotes apneic and lethal ventilatory arrest responses to hypoxia (5% O2 for 60 min) in rat pups. Here, we tested whether PNE‐induced apneic and lethal ventilatory arrest were of central origin without airway hyperreactivity (AHR). We further tested whether PNE enhanced pulmonary C neural response to capsaicin (CAP) associated with upregulation of TRPV1 in nodose ganglion neurons. In Ctrl and PNE‐treated pups, we recorded: i) diaphragm EMG during 5% O2 up to 60 min and ii) specific airway resistance (sRaw) response to increasing dose of aerosol methacholine (0, 3.125, 6.25, 12.5, 25 mg/ml) in conscious state; iii) pulmonary C neural response to right atrial bolus injection of CAP (1 μg/kg) in anesthetized and paralyzed state; and iv) TRPV1 mRNA expression in neurons of nodose ganglia (by RT‐PCR). PNE produced apnea and lethal ventilatory arrest concomitant with silence of diaphragm EMG and did not induce AHR. PNE increased pulmonary C neural firing response to CAP associated with upregulation of TRPV1 in nodose ganglia neurons. We conclude that PNE increases PCF sensitivity likely through increasing TRPV1 expression, contributing to the PNE‐promoted central origin of the apneic and lethal ventilatory arrest responses to hypoxia.Grant Funding Source: Supported by HL‐107462