title: NMDA as well as non-NMDA receptors in phrenic nucleus mediate respiratory effects of carotid chemoreflex.
abstract: An in vivo model was used to identify the transmitter/receptor mechanisms in the phrenic nucleus that mediate carotid chemoreceptor responses. Adult male Wistar rats, anesthetized with urethan, were fixed in a stereotaxic instrument, and the blood pressure and heart rate were monitored. The rats were immobilized and artificially ventilated to maintain the end-tidal CO2 at 4.5-5%. The vagus nerves were bilaterally sectioned, and a pneumothorax was produced. Activity was recorded from one of the phrenic nerves. The spinal cord was exposed from C1 to T1 vertebral level. The dorsal and ventral rootlets of spinal nerves C3, C5, and C6, ipsilateral to the phrenic nerve from which electrical activity was recorded, were sectioned; the dorsal and ventral roots of spinal nerve C4 were left intact. Thus the phrenic nerve bursts recorded in this preparation represented output from a portion of the phrenic nucleus located in the ipsilateral C4 spinal segment. Carotid chemoreceptor stimulation by N2 inhalation increased the amplitude as well as the frequency of phrenic nerve bursts. Microinjections (50 nl) of a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist (D(-)-2-amino-7-phosphonoheptanoic acid, AP-7, 50-100 mM) into the phrenic nucleus decreased the N2-induced increase in amplitude, but not the frequency, of phrenic nerve bursts. Likewise microinjections of a specific non-NMDA receptor antagonist (1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulfonamid e, NBQX, 0.5-1 mM) into the phrenic nucleus decreased the N2-induced increase in phrenic nerve burst amplitude. When AP-7 and NBQX were microinjected into the phrenic nucleus sequentially within an interval of 5 min, a drastic reduction in the N2-induced increase in phrenic nerve burst amplitude was observed. These observations suggest that both NMDA and non-NMDA receptors located in the phrenic nucleus are involved in the mediation of phrenic nerve responses to the carotid chemoreceptor stimulation.
authors.affiliation: Section of Neurological Surgery, New Jersey Medical School, Newark 07103, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Chitravanshi
authors.forename: H N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009333:Neck; D010791:Phrenic Nerve / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017459:Receptors, Amino Acid / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D012119:Respiration / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism* / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid