Abstract
L-Aspartate (L-ASP) acts as an excitatory amino acid neurotransmitter at the synapses of brain stem respiratory neurons. In order to determine the effect of L-ASP on the neonatal ventilatory response to hypoxia, 9 control piglets [age 4.3 ± (SD) 0.9 days, weight 1.9 ± 0.5 kg] and 9 L-ASP-treated animals [age 5.0 ± (SD) 1.4 days, weight 2.1 ± 0.7 kg] were studied. Minute ventilation, oxygen consumption, arterial blood pressure, and blood gases were measured in sedated piglets while spontaneously breathing room air and during 1, 5, and 10 min of hypoxia (O2 concentration in inspired gas 0.10). Measurements were obtained before and 60 min after the administration of L-ASP (580 mg/kg i.v. over 1 h) or 5% dextrose solution. In the control animals, the ventilatory response to hypoxia was similar before and after dextrose infusion. In contrast, a significant and sustained increase in ventilation was observed at 1, 5, and 10 min of hypoxia after the administration of L-ASP. Changes in oxygen consumption, heart rate, arterial blood pressure, pH, and arterial O2 tension with hypoxia were similar before and after the L-ASP infusion, while the arterial CO2 tension decreased significantly during hypoxia after the administration of L-ASP. These data suggest that the excitatory amino acid L-ASP is an important mediator of the hypoxic hyperventilation in the neonate. We speculate that the administration of exogenous L-ASP modifies the balance of central nervous system neurotransmitters during hypoxia, resulting in predominance of excitatory neurotransmission.
