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 (VE), 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 VE 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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AA:
-
amino acid
- ABP:
-
arterial blood pressure
- EOG:
-
electro-oculogram
- HR:
-
heart rate
- NTS:
-
nucleus tractus solitarius
- VE:
-
minute ventilation
- VT:
-
tidal volume
References
Sankaran K, Wiebe H, Seshia MM, Boychuk RB, Cates D, Rigatto H 1979 Immediate and late ventilatory response to high and low O2 in preterm infants and adults subjects. Pediatr Res 13: 875–878
Weil JV, Byrne-Quinn E, Sodal IE, Friesen WO, Underhill B, Filley GF, Grover RF 1970 Hypoxic ventilatory drive in normal man. J Clin Invest 49: 1061–1072
Suguihara C, Hehre D, Huang J, Devia C, Bancalari E 1996 Decreased ventilatory response to hypoxia in sedated newborn piglets prenatally exposed to cocaine. J Pediatr 128: 389–395
Georgopoulos D, Walker S, Anthonisen NR 1989 Increased chemoreceptor output and ventilatory response to sustained hypoxia. J Appl Physiol 67: 1157–1163
Lin J, Suguihara C, Huang J, Hehre D, Devia C, Bancalari E 1996 Effect of N-methyl-D-aspartate receptor blockade on hypoxic ventilatory response in unanesthetized piglets. J Appl Physiol 80: 1759–1763
Blanco CE, Hanson MA, Johnson P, Rigatto H 1984 Breathing pattern of kittens during hypoxia. J Appl Physiol 56: 12–17
Bureau MA, Begin R 1982 Postnatal maturation of the respiratory response to O2 in awake newborn lambs. J Appl Physiol 52: 428–433
Gozal D, Gozal E, Torres JE, Gozal YM, Nuckton TJ, Hornby PJ 1997 Nitric oxide modulates ventilatory responses to hypoxia in the developing rat. Am J Respir Crit Care Med 155: 1755–1762
Miller MJ, Haxhiu MA, Haxhiu-Poskurica B, Dreshaj IA, DiFiore JM, Martin RJ 2000 Recurrent hypoxia exposure and reflex responses during development in the piglet. Respir Physiol 123: 51–61
Akay M, Lipping T, Moodie K, Hoopes PJ 2002 Effects of hypoxia on the complexity of respiratory patterns during maturation. Early Hum Dev 70: 55–71
Moss IR, Runold M, Dahlin I, Fredholm BB, Nyberg F, Lagercrantz H 1987 Respiratory and neuroendocrine responses of piglets to hypoxia during postnatal development. Acta Physiol Scand 131: 533–541
Fisher JT, Mortola JP 1980 Statics of the respiratory system in newborn mammals. Respir Physiol 41: 155–172
Mortola JP, Rezzonico R 1988 Metabolic and ventilatory rates in newborn kittens during acute hypoxia. Respir Physiol 73: 55–68
Burton MD, Kazemi H 2000 Neurotransmitters in central respiratory control. Respir Physiol 122: 111–121
Navarro H, Suguihara C, Soliz A, Hehre D, Huang J, Bancalari E 1998 Effect of L-aspartate on the ventilatory response to hypoxia in sedated newborn piglets. Biol Neonate 73: 387–394
Huang J, Suguihara C, Hehre D, Lin J, Bancalari E 1994 Effects of GABA receptor blockade on the respiratory response to hypoxia in sedated newborn piglets. J Appl Physiol 77: 1006–1010
McCormick A, Suguihara C, Huang J, Devia C, Hehre D, Bruce J, Bancalari E 1998 Depressed ventilatory response to hypoxia in hypothermic newborn piglets: role of glutamate. J Appl Physiol 84: 830–836
Kazemi H, Hoop B 1991 Glutamic acid and gamma-aminobutyric acid neurotransmitters in central control of breathing. J Appl Physiol 70: 1–7
Soto-Arape I, Burton M, Kazemi H 1995 Central amino acid neurotransmitters and the hypoxic ventilatory response. Am J Respir Crit Care Med 151: 1113–1120
Sturman JA 1988 Taurine in development. J Nutr 118: 1169–1176
Phillipson EA, Bowes G 1986 Control of breathing during sleep. In: Cherniak NS, Widdicombe JG (eds) Handbook of Physiology. Sec. 3, Respiration. Control of Breathing, Vol. 2. American Physiological Society, Bethesda, MD, pp 649–689
Bowery N 1989 GABAB-receptors and their significance in mammalian pharmacology. Trends Pharmacol Sci 10: 401–407
Nicoll RA 1988 The coupling of neurotransmitter receptors to ion channels in the brain. Science 241: 545–551
Rivera C, Voipio J, Payne J, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K 1999 The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397: 251–255
Murakoshi T, Suzue T, Tamai S 1985 A pharmacological study on respiratory rhythm in the isolated brainstem-spinal cord preparation of the newborn rat. Br J Pharmacol 86: 95–104
Tabata M, Kurosawa H, Kikuchi Y, Hida W, Ogawa H, Okabe S, Tun Y, Hattori T, Shirato K 2001 Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats. Am J Physiol Regul Integr Comp Physiol 281: R1411–R1419
Hoop B, Beagle JL, Maher TJ, Kazemi H 1999 Brainstem amino acid neurotransmitters and hypoxic ventilatory response. Respir Physiol 118: 117–129
Xiao Q, Suguihara C, Hehre D, Devia C, Huang J, Bancalari E 2000 Effects of GABA receptor blockade on the ventilatory response to hypoxia in hypothermic newborn piglets. Pediatr Res 47: 663–668
Shank RP, Aprison MH 1970 The metabolism in vivo of glycine and serine in eight areas of the rat central nervous system. J Neurochem 17: 1461–1474
Lahoya JL, Benavides J, Ugarte M 1980 Glycine metabolism and glycine synthase activity during the postnatal development of rat brain. Dev Neurosci 3: 75–80
Benavides J, Lopez-Lahoya J, Valdivieso F, Ugarte M 1981 Postnatal development of synaptic glycine receptors in normal and hyperglycinemic rats. J Neurochem 37: 315–320
Carpenter MK, Parker I, Miledi R 1988 Expression of GABA and glycine receptors by messenger RNAs from the developing rat cerebral cortex. Proc R Soc Lond B Biol Sci 234: 159–170
Saransaari P, Oja SS 2000 Modulation of the ischemia-induced taurine released by adenosine receptors in the developing and adult mouse hippocampus. Neuroscience 97: 425–430
Ohtake PJ, Simakajornboon N, Fehniger MD, Xue YD, Gozal D 2000 N-Methyl-D-aspartate receptor expression in the nucleus tractus solitarii and maturation of hypoxic ventilatory response in the rat. Am J Respir Crit Care Med 162: 1140–1147
Toleikis JR, Wang L, Boyarsky LL 1979 Effects of excitatory and inhibitory amino acids on phasic respiratory neurons. J Neurosci Res 4: 225–235
Schlenker EH, Goldman M 1988 Acute effects of aspartic acid on ventilation of male and female rats. Physiol Behav 42: 313–318
Mayer CA, Haxhiu MA, Martin RJ, Wilson CG 2006 Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. J Appl Physiol 100: 91–97
Acknowledgements
The authors thank Jian Huang, M.D., for his technical assistance with the analysis of amino acids by HPLC.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the University of Miami Project: New Born.
Rights and permissions
About this article
Cite this article
Hehre, D., Devia, C., Bancalari, E. et al. Brainstem Amino Acid Neurotransmitters and Ventilatory Response to Hypoxia in Piglets. Pediatr Res 63, 46–50 (2008). https://doi.org/10.1203/PDR.0b013e31815b4421
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31815b4421
