“Full term” prenatal nicotinic exposure (fPNE) increases the pulmonary C‐fiber (PCF)‐mediated apneic response in rat pups

Abstract

Different from traditional PNE, fPNE consists of the periods before pregnancy and during pregnancy and lactation. Our recent study has shown that fPNE significantly depresses hypoxic ventilatory response (HVR) often followed by respiratory failure and death in postnatal rats (P12–14) (FASEB 2012, Xu and Zhuang), but the relevant mechanisms remain unexplored. PCFs are sensitized/stimulated by nicotine and inhibitory to ventilation and HVR. These results, along with an over‐expression of vagal C‐fibers in SIDS victims, allow us to hypothesize that fPNE would augment the PCF‐mediated apneic response via sensitizing PCFs and elevating PCF expression in the airways. We compared the ventilatory response to right atrial bolus injection of capsaicin (1 μg/kg) to stimulate PCFs in anesthetized fPNE and control pups, and then the PCF density in the airways was identified by using substance P immunoreactivity (SP‐IR). We also tested if fPNE was able to sensitize PCFs by extracellularly recording pulmonary C neurons (cell bodies of PCFs) in nodose ganglia of anesthetized and paralyzed control and fPNE pups. We found that fPNE: 1) significantly prolonged the apneic response to capsaicin by ~3‐fold with little change in baseline cardiorespiratory activities; 2) augmented pulmonary C neural firing response to capsaicin; and 3) markedly increased the SP‐IR fibers’ density in the airways. Our results suggest that fPNE augments the PCF‐mediated apneic response via sensitizing PCFs and elevating airway SP‐IR fibers’ density. Further studies are required for determining the role of PCFs in generating the depressed HVR and respiratory failure observed in fPNE pups. (Supported by HL 107462 and ALA RG‐191095‐N)