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.
Highlights
Acute exposure to hypoxia stimulates arterial carotid body chemoreceptors, which in turn mediate a reflex increase in breathing (Powell et al 1998)
We examined the effect of nucleus tractus solitarii (NTS)-specific microinjections of a cocktail of antagonists targeted to the three known types of ionotropic glutamatergic receptors (i.e., amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), N-methyl-D-aspartate receptor (NMDAR), and kainate receptors [KARs]) on the acute hypoxic ventilatory response (HVR) and ventilatory acclimatization to hypoxia (VAH) in conscious rats acclimatized to sea level or hypobaric hypoxia (PIO2 = 70 mmHg) for 7–9 days
We showed different effects of NMDAR versus AMPAR blockade in the NTS on the HVR and on VAH (Pamenter et al 2014)
Summary
Acute exposure to hypoxia stimulates arterial carotid body chemoreceptors, which in turn mediate a reflex increase in breathing (i.e., the hypoxic ventilatory response [HVR]) (Powell et al 1998). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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