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?_E), tidal volume (V_T), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O₂) 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?_E either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, N_M failed to alter V?_E in obese rats. In contrast, N_HCl significantly (p < 0.05) increased V?_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?_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?_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.