Brain γ-aminobutyric acid (GABA) levels increase during hypoxia which may modulate the ventilatory response to hypoxia. To test the possibility that the depressed neonatal ventilatory response to hypoxia may be related to increased central nervous system GABA activity, 26 sedated spontaneously breathing newborn piglets (age 5 ± 1 day, wt 1.7 ± 0.4 kg) were studied. Minute ventilation (V̇E), oxygen consumption, heart rate, arterial blood pressure, and arterial blood gases were measured in room air and after 1, 5, and 10 min of hypoxia (inspired O3 fraction 0.10) before drug intervention. Immediately after these measurements, an infusion of saline or the GABA. α- receptor blocker (bicuculline, 0.3 mg/kg iv) or β-receptor blocker (CGP- 35348, 100-300 mg/kg iv) was administered while animals were hypoxic. All measurements were repeated at 1, 5, and 10 min after initiation of the drug infusion. Basal V̇E was similar among groups. During hypoxia, V̇E increased significantly in the animals that received either a GABA α- or β-receptor blocker but not in those receiving saline. Changes in arterial PO2, oxygen consumption, heart rate, and arterial blood pressure were similar among groups before and after saline or GABA antagonist infusion. These results suggest that the decrease in ventilation during the biphasic ventilatory response to hypoxia in the neonatal piglet is in part mediated through the depressant effect of GABA on the central nervous system.
- γ-aminobutyric acid antagonist
- CGP- 35348
- newborn animal
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation