Dopaminergic modulation of ventilation in obese Zucker rats

1 First Department of Medicine, Asahikawa Medical College, Asahikawa, 078-8510, Japan; and 2 Department of Physical Therapy, Exercise and Nutrition Sciences, and Center for Sleep Disorders Research, University at Buffalo, State University of New York, Buffalo, New York 14214-3079 To investigate the hypothesis that the impaired respiratory drive noted in morbid obesity was attributable to altered dopaminergic mechanisms acting on peripheral and/or central chemoreflex sensitivity, seven obese and seven lean Zucker rats were studied at 11 wk of age. Ventilation ( E ) was measured by the barometric technique during hyperoxic (100% O 2 ), normoxic (21% O 2 ), hypoxic (10% O 2 ), and hypercapnic (7% CO 2 ) exposures after the administration of vehicle (control), haloperidol [Hal, 1 mg/kg, a central and peripheral dopamine (Da) receptor antagonist], or domperidone (Dom, 0.5 mg/kg, a peripheral Da receptor antagonist). In both lean and obese rats, Hal increased tidal volume and decreased respiratory frequency during hyperoxia or normoxia, resulting in an unchanged E . In contrast, Dom did not affect tidal volume, frequency, or E during hyperoxia or normoxia. During hypoxia, however, E significantly increased from 1,132 ± 136 to 1,348 ± 98 ml · kg 1 · min 1 ( P