Opioidergic modulation of ventilatory response to sustained hypoxia in obese Zucker rats

Objective: To determine whether altered central and/or peripheral opioidergic mechanisms contribute to the altered ventilatory response to sustained hypoxia in obese Zucker rats. Research Methods and Procedures: Eight lean (176 +/- 8 [SEM] g) and eight obese (225 +/- 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary Ventilation (V(over dot)(E)) tidal volume (V-T), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O-2) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (N-M; 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (N-HCl; 5 mg/kg, peripheral and central opioid antagonist). Results: Administration of N-M and N-HCl in lean animals had no effect on V(over dot)(E) either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, N-M failed to alter V(over dot)(E) in obese rats. In contrast, N-HCl significantly (p < 0.05) increased V(over dot)(E), and V-T both at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, V-T remained elevated with N-HCl, but the earlier elevation of V(over dot)(E) seemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia. Discussion: Thus, endogenous opioids modulate both resting V(over dot)(E) and the ventilatory response to sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically on opioid receptors located within the central nervous system.