title: The effect of combined glutamate receptor blockade in the NTS on the hypoxic ventilatory response in awake rats differs from the effect of individual glutamate receptor blockade.
abstract: Ventilatory acclimatization to hypoxia (VAH) increases the hypoxic ventilatory response (HVR) and causes persistent hyperventilation when normoxia is restored, which is consistent with the occurrence of synaptic plasticity in acclimatized animals. Recently, we demonstrated that antagonism of individual glutamate receptor types (GluRs) within the nucleus tractus solitarii (NTS) modifies this plasticity and VAH (J. Physiol. 592(8):1839-1856); however, the effects of combined GluR antagonism remain unknown in awake rats. To evaluate this, we exposed rats to room air or chronic sustained hypobaric hypoxia (CSH, PiO2 = 70 Torr) for 7-9 days. On the experimental day, we microinjected artificial cerebrospinal fluid (ACSF: sham) and then a "cocktail" of the GluR antagonists MK-801 and DNQX into the NTS. The location of injection sites in the NTS was confirmed by glutamate injections on a day before the experiment and with histology following the experiment. Ventilation was measured in awake, unrestrained rats breathing normoxia or acute hypoxia (10% O2) in 15-min intervals using barometric pressure plethysmography. In control (CON) rats, acute hypoxia increased ventilation; NTS microinjections of GluR antagonists, but not ACSF, significantly decreased ventilation and breathing frequency in acute hypoxia but not normoxia (P < 0.05). CSH increased ventilation in hypoxia and acute normoxia. In CSH-conditioned rats, GluR antagonists in the NTS significantly decreased ventilation in normoxia and breathing frequency in hypoxia. A persistent HVR after combined GluR blockade in the NTS contrasts with the effect of individual GluR blockade and also with results in anesthetized rats. Our findings support the hypotheses that GluRs in the NTS contribute to, but cannot completely explain, VAH in awake rats.
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, La Jolla, California Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pamenter
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Jetson
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: John A
authors.initials: JA
authors.lastname: Carr
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Powell
keywords: AMPA receptors; NMDA receptors; hypercapnic ventilatory response; kainate receptors
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