Acute effects of aspartic acid on ventilation of male and female rats

Schlenker, Evelyn H.; Goldman, Max

doi:10.1016/0031-9384(88)90271-5

Cited by 13 publications

(5 citation statements)

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“…The significant increase in the ventilatory response to hypoxia in newborn piglets after L-ASP infusion is in disagreement with that described in adult rats who showed a similar increase in V E at 10 min of hypoxia after aspartic acid or placebo infusion [12]. However, the control animals displayed a marked hypoxic hyperventilation (2.5-fold increase) which may be close to the limit of their ventilatory capacity.…”

Section: Discussioncontrasting

confidence: 54%

“…A significant decrease in V E was observed 45 min after aspartic acid (580 mg/ kg i.p.) administration in adult male rats, while a significant increase in V E was observed in female rats after the drug infusion [12]. The different ventilatory response according to gender observed in adult rats may be peculiar to this animal species.…”

Section: Discussionmentioning

confidence: 80%

“…However, intravenous administration of aspartic acid to adult rats resulted in a significant increase in basal ventilation only in female rats. The ventilatory response to hypoxia and hypercapnia was not modified by aspartic acid infusion [12]. To the best of our knowledge, no studies have been published evaluating the role of L-ASP on the neonatal ventilatory response to hypoxia.…”

Section: Introductionmentioning

confidence: 86%

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Effect of L-Aspartate on the Ventilatory Response to Hypoxia in Sedated Newborn Piglets

et al. 1998

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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.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 86%

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Effect of L-Aspartate on the Ventilatory Response to Hypoxia in Sedated Newborn Piglets

et al. 1998

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“…The excitatory effect of aspartate on the respiratory system has been reported in adult cats and rats (35,36). In the neonatal piglets, Navarro et al (15) administered L-aspartate and produced a significant increase in the ventilatory response to hypoxia, confirming the excitatory effect this AA has on respiratory control.…”

Section: Discussionmentioning

confidence: 86%

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

et al. 2008

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ABSTRACT:The ventilatory response to hypoxia is influenced by the balance between inhibitory (GABA, glycine, and taurine) and excitatory (glutamate and aspartate) brainstem amino acid (AA) neurotransmitters. To assess the effects of AA in the nucleus tractus solitarius (NTS) on the ventilatory response to hypoxia at 1 and 2 wk of age, inhibitory and excitatory AA were sampled by microdialysis in unanesthetized and chronically instrumented piglets. Microdialysis samples from the NTS area were collected at 5-min intervals and minute ventilation (V E ), arterial blood pressure (ABP), and arterial blood gases (ABG) were measured while the animals were in quiet sleep. A biphasic ventilatory response to hypoxia was observed in wk 1 and 2, but the decrease in V E at 10 and 15 min was more marked in wk 1. This was associated with an increase in inhibitory AA during hypoxia in wk 1. Excitatory AA levels were elevated during hypoxia in wk 1 and 2. Changes in ABP, pH, and ABG during hypoxia were not different between weeks. These data suggest that the larger depression in the ventilatory response to hypoxia observed in younger piglets is mediated by predominance of the inhibitory AA neurotransmitters, GABA, glycine, and taurine, in the NTS. T he difference in ventilatory response to hypoxia between neonatal and adult subjects is well documented (1-3). The ventilatory response to hypoxia during the neonatal period is characterized by an increase in ventilation (1-2 min) followed by a decrease in minute ventilation (V E ) to values below or close to baseline levels. In contrast, a more sustained ventilatory response to hypoxia is described in adults (4). The initial increase in ventilation is mediated by the peripheral chemoreceptors, whereas subsequent changes are centrally mediated (5,6).The change from the neonatal to the adult ventilatory response is thought to occur during early postnatal life in most species (7,8). Previous studies have demonstrated that this change in the ventilatory response occurs within the first 1-2 wk of life in piglets (9 -11).Several mechanisms may be responsible for the ventilatory depression observed during hypoxia soon after birth. These include deterioration in lung mechanics (12), changes in metabolism (13), and a predominance of inhibitory over excitatory neurotransmitters in the CNS (14). Previous studies from our laboratory have demonstrated a role for amino acids (AA) in the hypoxic ventilatory response in newborn animals (5,(15)(16)(17). The balance between excitatory AA, such as glutamate and aspartate, and inhibitory AA, such as GABA and glycine, may influence the ventilatory response to hypoxia in the neonatal and postnatal periods. In newborn animals, it has been suggested that the increase in the release of the CNS inhibitory amino acid neurotransmitter GABA may be responsible for the hypoxic ventilatory depression (9,16,18). However, it is also possible that the biphasic response in ventilation during hypoxia may be due to a reduction in the release of central excitatory AA neur...

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“…Gender differences associated with NMDA function in the control of breathing have only been studied indirectly. For example, Schlenker and Goldman (22) showed that neonatal treatment of rats with aspartic acid (which acts on NMDA receptors) results in adult male rats that exhibit alveolar hypoventilation and blunted ventilatory responses to hypercapnia. Female rats treated in a similar manner did not exhibit these abnormalities relative to vehicle-treated female rats.…”

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confidence: 99%

Dextromethorphan affects ventilation differently in male and female rats

Schlenker

1996

Journal of Applied Physiology

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Subcutaneous administration of aspartic acid results in a long-lasting but reversible depression of ventilation in male but not in female rats. Aspartic acid acts on N-methyl-D-aspartate receptors. The present study tested the hypothesis that a noncompetitive N-methyl-D-aspartate-receptor antagonist, dextromethorphan (Dex), would depress ventilation in female rats and stimulate it in male rats. Moreover, Dex administered prior to aspartic acid should prevent the aspartic acid-induced depression of ventilation in male rats. In female rats, Dex caused a 30% depression of ventilation relative to saline at 5 and 10 mg/kg (P < 0.01) but not at the highest dose (20 mg/kg). In male rats, Dex had no effect on ventilation. At a dose of 20 mg/kg, Dex depressed oxygen consumption to 50% of the saline value at all time points in female rats (P < 0.001) and in male rats 45 and 60 min after administration. The time points when Dex depressed ventilation and oxygen consumption were different in female rats, suggesting that the depression of ventilation was not the result of a depression in oxygen consumption. During a hypercapnic challenge (7% CO2), female rats treated with 5 and 10 mg/kg of Dex exhibited a smaller increase in ventilatory response relative to saline treatment. At a dose of 20 mg/kg, the hypercapnic responsiveness of male rats was markedly stimulated (85.8 +/- 8.95 ml/min) relative to saline (50.6 +/- 9.14 ml/min; P < 0.001). Finally, Dex administered before aspartic acid prevented the aspartic acid-induced depression of ventilation in male rats. Thus, in rats, Dex has gender-specific effects on ventilation and these effects are not associated with changes in oxygen consumption.

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Acute effects of aspartic acid on ventilation of male and female rats

Cited by 13 publications

References 14 publications

Effect of L-Aspartate on the Ventilatory Response to Hypoxia in Sedated Newborn Piglets

Effect of L-Aspartate on the Ventilatory Response to Hypoxia in Sedated Newborn Piglets

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

Dextromethorphan affects ventilation differently in male and female rats

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