Chronic Hypoxia Blunts the Hypoxic Ventilatory Response in Neonatal and Adult Rats

Abstract

Chronic hypoxia (CH) may affect the control of breathing differently in neonatal versus adult mammals. It is widely accepted that CH blunts the hypoxic ventilatory response (HVR) in neonatal rats but augments hypoxic ventilation in adult rats. However, there is also evidence that longer durations of CH can progressively attenuate the HVR in adult rats too. Therefore, we predicted that short durations of CH (3 days) would blunt the HVR in neonatal rats and augment the HVR in adult rats, but that longer durations of CH (7 days) would blunt the HVR in adult rats. To test these predictions, rats were exposed to 12% O2 (CH) or room air (Control) for 3 days as neonates (from P0 to P3, or from P7 to P10) or as young adults. Baseline ventilation (21% O2) and the acute HVR (12% O2) were measured by plethysmography immediately following the exposure. The adult rats were then returned to the CH and Control chambers for 4 more days before repeating the breathing measurements. Although Sprague‐Dawley rats were used in all experiments, adults from two different commercial suppliers (Charles River Laboratories and Envigo) were used to determine whether genetic background might influence the results. Baseline ventilation was greater in all CH groups regardless of their age, consistent with ventilatory acclimatization. With the exception of CH rats at P10 in which peak hypoxic ventilation (i.e., minute ventilation during the first minute of 12% O2) was also greater than in Controls, hypoxic ventilation was generally similar between CH and Control groups or reduced in the CH group. Accordingly, the change in ventilation from baseline (i.e., HVR) was blunted by CH regardless of the age of the rats, the duration of the CH exposure (adults only), or the substrain of Sprague‐Dawley rat (adults only). The order in which test gases were presented during breathing measurements (i.e., 21% O2 – 12% O2 vs. 12% O2 – 21% O2) did not influence the calculated HVR in adult rats. We conclude that the respiratory plasticity elicited by normobaric CH is similar across ages in Sprague‐Dawley rats.