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GABA_A and GABA_B receptors differentially modulate volume and frequency in ventilatory compensation in obese Zucker rats

¹Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ²Department of Early Childhood Education, National Taichung University, Taichung, Taiwan; ³Department of Physical Medicine and Rehabilitation, Chung-Shan Medical University Hospital, Taichung, Taiwan; and ⁴Department of Physiology, ⁵Graduate Institute of Chinese Medical Science, and ⁶Department of Physical Therapy, China Medical University, Taichung, Taiwan

Submitted 21 November 2005 ; accepted in final form 16 August 2006

The aim of this study was to investigate whether GABA_A and/or GABA_B receptor-mediated mechanisms contribute to the impaired ventilatory response and reduced maximal aerobic exercise capacity in obese Zucker rats. Ten lean and 10 obese Zucker rats were studied at 12 wk of age. Minute ventilation (E), tidal volume (VT), and breathing frequency (f) during room air breathing and in response to 10 min of hypercapnia (8% CO₂) and 30 min of hypoxia (10% O₂) were measured by the barometric method, and peak oxygen consumption (O_{2 peak}) was measured by an enclosed metabolic treadmill following the randomized blinded subcutaneous administration of equal volumes of DMSO (vehicle), bicuculline (selective GABA_A receptor antagonist, 1 mg/kg), and phaclofen (selective GABA_B receptor antagonist, 1 mg/kg). Administration of bicuculline and phaclofen to lean animals had no effect on E and O_{2 peak}. Similarly, phaclofen failed to alter E and O_{2 peak} in obese rats, although it did significantly increase f after 5–20 min of hypoxia. In contrast, bicuculline increased E and VT relative to DMSO during room air breathing and after 10–30 min of hypoxic exposure in obese rats, but it did not increase E at 5 min of hypoxemia. Bicuculline increased O_{2 peak} relative to DMSO in obese Zucker rats. We conclude that endogenous GABA acting on GABA_A receptors can modulate E and O_{2 peak} in obese but not in lean Zucker rats, whereas endogenous GABA acting on GABA_B receptors modulates f during hypoxia (5–20 min) in obese rats in a very different manner from that when acting on GABA_A receptors.

gamma-aminobutyric acid; respiration; bicuculline; phaclofen; hypoxia