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NMDA receptor-mediated modulation of ventilation in obese Zucker rats

International Journal of Obesity volume 25, pages 997–1004 (2001)Cite this article

Abstract

BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans and is believed to represent part of the pathogenesis of obesity hypoventilation syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to the release of excitatory neurotransmitters, in particular glutamate, acting specifically on N-methyl-D-aspartate (NMDA) receptors.

OBJECTIVES: The aim of the present study was to investigate whether NMDA receptor-mediated mechanisms are responsible for the altered ventilatory response to sustained hypoxia observed in obese Zucker (Z) rats.

SUBJECTS: Seven lean and seven 15-week-old obese male Z rats were studied.

MEASUREMENTS: Ventilation (V̇E) at rest and during 30 min sustained hypoxic (10% O2) exposure was measured by the barometric method. V̇E was assessed following the blinded-random administration of equal volumes of either saline (vehicle) or dextromethorphan (DM, 10 mg/kg), a non-competitive glutamate NMDA receptor antagonist.

RESULTS: DM had no effects on resting V̇E in both lean and obese rats during room air breathing. Lean rats treated with DM exhibited a significant (P<0.05) depression in V̇E, VT, and VT/TI during either the early (5 min) or the late phase (30 min) of ventilatory response to sustained hypoxia. In contrast, DM administration in obese rats did not change V̇E, VT, or VT/TI during the early phase of ventilatory response to hypoxia. During the late phase of ventilatory response to hypoxia. obese rats treated with DM exhibited a similar depression in V̇E and VT as observed in lean rats, but had no significant change in VT/TI during the 30 min hypoxic exposure.

CONCLUSION: Our findings indicate that altered glutamatergic mechanisms acting on NMDA receptors are partially responsible for a blunted early phase of ventilatory response to hypoxia noted in obese rats and also contribute to their reduced neural respiratory drive.

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Acknowledgements

The present study was supported by research grant no. AG-16048 from the National Institutes of Health. GA Farkas is the recipient of a Career Investigator Award from the American Thoracic Society

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  1. Department of Physical Therapy, Exercise, and Nutrition Science, University at Buffalo, The State University of New York, Buffalo, New York, USA

    SD Lee, H Nakano & GA Farkas

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  1. SD Lee
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Correspondence to GA Farkas.

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Lee, S., Nakano, H. & Farkas, G. NMDA receptor-mediated modulation of ventilation in obese Zucker rats. Int J Obes 25, 997–1004 (2001). https://doi.org/10.1038/sj.ijo.0801663

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