Endogenous Opioids Modulate Ventilation and Peak Oxygen Consumption in Obese Zucker Rats

Levels of endogenous opioids are increased in morbidly obese humans and obese rats. Endogenous opioids are important neuromodulators, and are involved in a wide range of functions including ventilatory control. We studied eight lean and eight obese Zucker (Z) rats at 6 and 16 wk of age. We assessed minute ventilation (V E) at rest and during hypercapnic challenges, as well as peak oxygen consumption (V O(2peak)) after the administration of saline (control), naloxone hydrochloride (N(HCl)), and naloxone methiodide (N(M)). Administration of N(HCl) and N(M) to lean animals had no effect on V E and V O(2peak). Similarly, N(M) failed to alter V E and V O(2peak) in obese rats studied at 6 or 16 wk of age. In young obese rats, N(HCl) significantly (p < 0.05) increased resting V E (721 +/- 154 [mean +/- SD] ml/kg/min versus 937 +/- 207 ml/kg/min, saline versus N(HCl), respectively); VE in response to 4% CO(2) (924 +/- 110 ml/kg/min versus 1,212 +/- 172 ml/ kg/min); V E in response to 8% CO(2) (1,233 +/- 172 ml/kg/min versus 1,565 +/- 327 ml/kg/min); and V O(2peak) (90.8 +/- 9.6 ml/kg(0.75)/min versus 98.3 +/- 5.9 ml/kg(0.75)/min). However, N(HCl) administration had no effect on V E or V O(2peak) in obese rats retested at 16 wk of age. Thus, endogenous opioids modulate resting ventilation, ventilatory responsiveness to CO(2), and V O(2peak) in young obese rats by acting specifically on receptors located within the central nervous system. This modulation disappears once the animals reach 16 wk of age.