Neonatal stress and abnormal hypercapnic ventilatory response of adult male rats: The role of central chemodetection and pulmonary stretch receptors

Neonatal maternal separation (NMS) is a form of stress that interferes with respiratory control development. At adulthood, the hypercapnic ventilatory response (HCVR) of male NMS rats is lower than controls both during wakefulness and anesthesia. To address the mechanisms underlying the respiratory phenotype of NMS rats, we first used phrenic nerve recording in anesthetised (urethane: 1.0 g/kg + isoflurane: 0.5%), vagotomised, and artificially ventilated (hyperoxic) animals, to test the hypothesis that the central chemodetection is altered by NMS. As no difference was observed between groups, we then tested the hypothesis that NMS affects respiratory modulation by pulmonary stretch receptors (PSRs). Experiments were performed on urethane/isoflurane anesthetised, spontaneously breathing rats (with vagi intact). The role of PSR and their implication was assessed during normo- and hypercapnia (+10 mm Hg above baseline) by the induction of a positive airway pressure (Paw). The slopes of the relationships between the ventilatory variables (frequency, amplitude, and minute activity) and the different levels of Paw in each group were compared between groups. During normocapnia, the decrease in breathing frequency induced by increasing Paw was greater in control than in NMS rats, thereby revealing that NMS reduces the Hering-Breuer reflex (HBR). During hypercapnia, however, the responses of control and NMS rats were similar indicating that the stimulation of chemoreceptors by CO2 reduced the influence of stretch receptors on ventilation. These results indicate NMS does not affect central CO2 chemosensitivity of this preparation but that differences in PSR function and/or signal integration contribute to the effects of NMS on respiratory regulation.