Neonatal stress and attenuation of the hypercapnic ventilatory response in adult male rats: the role of carotid chemoreceptors and baroreceptors

Abstract

Neonatal maternal separation (NMS) is a form of stress that disrupts respiratory control development. Awake adult male rats previously subjected to NMS show a ventilatory response to hypercapnia (HCVR; Fi(CO(2)) = 0.05) 47% lower than controls; however, the underlying mechanisms are unknown. To address this issue, we first tested the hypothesis that carotid bodies contribute to NMS-related attenuation of the HCVR by using carotid sinus nerve section or Fi(O(2)) manipulation to maintain Pa(O(2)) constant (iso-oxic) during hypercapnic hyperpnea. We then determined whether NMS-related augmentation of baroreflex sensitivity contributes to the reduced HCVR in NMS rats. Nitroprusside and phenylephrine injections were used to manipulate arterial blood pressure in both groups of rats. Pups subjected to NMS were separated from their mother 3 h/day from postnatal days 3 to 12. Control rats were undisturbed. At adulthood, rats were anesthetized [urethane (1g/kg) + isoflurane (0.5%)], and diaphragmatic electromyogram (dEMG) was measured under baseline and hypercapnic conditions (Pa(CO(2)): 10 Torr above baseline). The relative minute activity response to hypercapnia of anesthetized NMS rats was 34% lower than controls. Maintaining Pa(O(2)) constant during hypercapnia reversed this phenotype; the HCVR of NMS rats was 45% greater than controls. Although the decrease in breathing frequency during baroreflex activation was greater in NMS rats, the change observed within the range of pressure change observed during hypercapnia was minimal. We conclude that NMS-related changes in carotid body sensitivity to chemical stimuli and/or its central integration is a key mechanism in the attenuation of HCVR by NMS.