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

Objective: To determine whether altered central and/or peripheral opioiderg ic mechanisms contribute to the altered ventilatory response to sustained h ypoxia in obese Zucker rats. Research Methods and Procedures: Eight lean (176 +/- 8 [SEM] g) and eight o bese (225 +/- 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary V entilation (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) challe nges were measured on three separate occasions by the barometric method aft er the randomized, blinded administration of equal volumes of saline (contr ol), naloxone methiodide (N-M; 5 mg/kg, peripheral opioid antagonist), or n aloxone hydrochloride (N-HCl; 5 mg/kg, peripheral and central opioid antago nist). 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 co ntrast, N-HCl significantly (p < 0.05) increased V(over dot)(E), and V-T bo th at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. Af ter 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) a nd 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.