Apnea - the temporary cessation of respiratory airflow - is a common cause of intermittent hypoxia (IH) in premature infants. We hypothesized that IH elicits a stress response and alters glucose homeostasis in the neonatal rat. Rat pups were studied on postnatal day (PD) 2, 8, 10, 12, and14. Pups were exposed to normoxia (control) or 6 cycles consisting of 30 s exposures to hypoxia (FiO2=3%) over a 60 min period. Blood samples were obtained at baseline, after the 3rd cycle (~30 min), and after the 6th cycle (~60 min). Tissue samples were collected following the 6th cycle. Plasma ACTH, corticosterone, glucose, and insulin were analyzed at all ages. Hypothalamic, pituitary, and adrenal mRNA expression was evaluated by qPCR in PD2, PD8, and PD12 pups. Exposure to IH elicited significant increases in plasma ACTH and corticosterone at all ages studied. The largest increase in corticosterone occurred in PD2 pups, despite only a very small increase in plasma ACTH. This ACTH-independent increase in corticosterone in PD2 pups was associated with increases in adrenal Ldlr and Star mRNA expression. Additionally, IH caused hyperglycemia and hyperinsulinemia at all ages. We conclude that IH elicits a significant pituitary-adrenal response and significantly alters glucose homeostasis. Furthermore, the quantitative and qualitative characteristics of these responses depend on developmental age.
- Hypothalamic-pituitary-adrenal axis
- adrenal cortex
- Copyright © 2013, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology