Phrenic and sympathetic nerve responses to glutamergic blockade during normoxia and hypoxia.
Because hypoxia increases brain extracellular glutamate levels, we hypothesized that gasping and increased sympathetic activity during severe hypoxia result from glutamergic excitation. To test this hypothesis, we exposed anesthetized paralyzed vagotomized glomectomized cats to hypoxia before and after N-methyl-D-aspartate (NMDA) glutamergic blockade (MK-801, 1 mg/kg iv) or non-NMDA blockade (NBQX, 3 mg/kg iv) while monitoring phrenic neurogram (PN) and inspiratory-synchronous (ISSN) and tonic (TSN) activity in cervical sympathetic neurogram (SN). Before hypoxia, MK-801 caused apneusis and reduced PN and ISSN amplitude by 38 and 84%, respectively, but TSN activity was unaffected. During hypoxia, MK-801 had no effect on PN gasping or TSN activity but reduced ISSN amplitude during gasping. Before hypoxia, NBQX reduced PN and ISSN amplitude by 54 and 60%, respectively but did not affect inspiratory timing or TSN activity. Gasping activity in PN and ISSN and TSN activity during hypoxia were unaffected by NBQX. We conclude that 1) ionotropic glutamergic receptor activation is important for eupneic phrenic patterning but is not involved in genesis of gasping, 2) NMDA receptor activation is involved in integration of respiratory and sympathetic activity, and 3) changes in TSN activity are independent of ionotropic glutamergic receptor activation.
Department of Medicine, University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School, New Brunswick 08903-0019.
L O
LO
Chae
J E
JE
Melton
J A
JA
Neubauer
N H
NH
Edelman
D000818:Animals; D002415:Cats; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010791:Phrenic Nerve / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate