Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats

Tabata, Masao; Kurosawa, Hájíme; Kikuchi, Yoshihiro; Hida, Wataru; Ogawa, Hiroyasu; Okabe, Shinichi; Tun, Ye; Hattori, Toshio; Shirato, Kunio

doi:10.1152/ajpregu.2001.281.5.r1411

Cited by 61 publications

(59 citation statements)

References 36 publications

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“…Similar to these results, Tabata et al (26) measured GABA concentrations during hypoxia from the NTS and showed a marked increase in GABA after 15 min of hypoxia in adult rats.…”

Section: Discussionsupporting

confidence: 66%

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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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“…Similar to these results, Tabata et al (26) measured GABA concentrations during hypoxia from the NTS and showed a marked increase in GABA after 15 min of hypoxia in adult rats.…”

Section: Discussionsupporting

confidence: 66%

“…It has been well documented that central amino acids change concentrations during hypoxia, and several studies have demonstrated that GABA is a major inhibitory amino acid neurotransmitter and is a central depressant of ventilation (18,19,26,27).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

et al. 2008

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“…Severe hypoxia could cause apnea, that is, hypoxic-induced apnea (Guntheroth and Kawabori 1975;Fewell et al 2005). Although the mechanism of hypoxic-induced apnea is not known, we speculate that central hypoxic depression may result from a positive feedback mechanism (Tabata et al 2001) inducing apnea, or that hyperventilation during hypoxic loading may induce apnea in the same manner as post-hyperventilation apnea induced by hypocapnia below the apneic threshold (Meah and Gardner 1994).…”

Section: Discussionmentioning

confidence: 94%

“…On the other hand, in the decline phase of ventilation during sustained hypoxic loading, γ -aminobutyric acid (GABA), which is an inhibitory transmitter, in the NTS had an important role in the hypoxic ventilatory decline after sustained hypoxic loading (Tabata et al 2001). Whether a GABAergic mechanism affects the onset of apnea under severe hypoxic stress is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The targeted fraction concentration of O 2 or CO 2 was obtained within 20 sec, and maintained for 3 min. The ventilatory responses to hypoxia were measured for 15 ~ 20 sec at the peak response during 3 min and those to hypercapnia were measured for the last 15 ~ 20 sec during 3 min (Mizusawa et al 1994;Ogawa et al 1995;Tabata et al 2001;Adachi et al 2004), with an interval of at least 30 min and in random order.…”

Section: Acute Hypoxic and Hypercapnic Ventilatory Responsesmentioning

confidence: 99%

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Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

Adachi

Ogawa

Okabe

et al. 2006

Tohoku J. Exp. Med.

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Hypoxia causes a life-threatening situation, and the ventilatory response to hypoxia plays an important role in preventing death. We have hypothesized that persons with a blunted hypoxic ventilatory response may have a weak defense response to hypoxic episodes and be susceptible to fatal respiratory disturbances. However, precise correlations between the hypoxic ventilatory response and respiratory disturbances are not well understood. In the present study we examined the hypoxic and hypercapnic ventilatory responses in nine inbred mouse strains (A/J, AKR/N, BALB/c, C3H/He, C57BL/6, DBA/2, NZW, SWR/J, and 129Sv). Breathing frequency, tidal volume and minute ventilation of unanesthetized and unrestrained mice were assessed by whole body plethysmography. Age-matched mice were exposed for 3 min to 10% O 2 in N 2 gas or 10% CO 2 in hyperoxic gas to determine the acute ventilatory response to chemical stimuli. Basal respiratory variables and hypoxic ventilatory responses differed among the strains, but the hypercapnic ventilatory response did not differ. The hypoxic ventilatory response was the highest in AKR/N mice and the lowest in SWR/J mice. These findings suggest that genetic factors may have influenced the hypoxic ventilatory response but not the hypercapnic ventilatory response. To examine the effects of severe hypoxic stress on the respiratory cycle, we exposed the strain with the highest or lowest hypoxic ventilatory response to 6% O 2 in N 2 until the onset of apnea. The "appearance time of apnea", which is defined as the time from the hypoxic loading to the onset of apnea, was shorter in the SWR/J strain than in the AKR/N strain. We suggest that a lower hypoxic ventilatory response may be a risk factor for apnea under hypoxia.

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Respiratory effects of cyanide

Eisenkraft

Falk

Bentur

2015

Toxicology of Cyanides and Cyanogens

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Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats

Cited by 61 publications

References 36 publications

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets

Mice with Blunted Hypoxic Ventilatory Response are Susceptible to Respiratory Disturbance during Hypoxia

Respiratory effects of cyanide

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