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Vol. 84, Issue 3, 853-861, March 1998
1 Department of Physical Therapy and Exercise Science, State University of New York at Buffalo, Buffalo, New York 14214; and 2 Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of Pediatrics and Physiology, and Tulane University School of Medicine, New Orleans, Louisiana 70112
N-methyl-D-aspartate
(NMDA) glutamate receptors mediate critical components of
cardiorespiratory control in anesthetized animals. The role of NMDA
receptors in the ventilatory responses to peripheral and central
chemoreceptor stimulation was investigated in conscious, freely
behaving rats. Minute ventilation
(
E)
responses to 10% O2, 5%
CO2, and increasing intravenous
doses of sodium cyanide were measured in intact rats before and after
intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume
(VT) decreased while frequency
increased, resulting in a modest reduction in
E.
Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The
E responses
to hypercapnia were qualitatively similar in control and MK-801
conditions, with slight reductions in respiratory drive (VT/TI)
after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was
unaffected. Sodium cyanide doses associated with significant
E
increases were 5 and 50 µg/kg before and after MK-801,
respectively. Thus 1-log shift to the right of individual dose-response
curves occurred with MK-801. Selective carotid body denervation reduced
E during
hypoxia by 70%, and residual hypoxic ventilatory responses were
abolished after MK-801. These findings suggest that, in conscious rats,
carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory
responses are critically dependent on NMDA receptor activation and that
NMDA receptor mechanisms are only modestly involved during hypercapnia.
hypoxia; hypercapnia; glutamate receptors; carotid body denervation; blood pressure
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