Endogenous opioids modulate ventilation and peak oxygen consumption in obese Zucker rats

Levels of endogenous opioids are increased in morbidly obese humans and obe se rats. Endogenous opioids are important neuromodulators, and are involved in a wide range of functions including ventilatory control. We studied eig ht lean and eight obese Zucker (Z) rats at 6 and 16 wk of age. We assessed minute ventilation ((V) over dot E) at rest and during hypercapnic challeng es, as well as peak oxygen consumption ((V) over dot O-2peak) after the adm inistration of saline (control), naloxone hydrochloride (N-HCl), and naloxo ne methiodide (N-M). Administration of N-HCl and N-M to lean animals had no effect on (V) over dot E and (V) over dot O-2peak. Similarly, N-M failed t o alter (V) over dot E and (V) over dot O-2peak in obese rats studied at 6 or 16 wk of age. In young obese rats, N-HCl significantly (p < 0.05) increa sed resting (V) over dot E (721 +/- 154 [mean +/- SD] ml/kg/min versus 937 +/- 207 ml/kg/min, saline versus N-HCl, respectively); VE in response to 4% CO2 (924 +/- 110 ml/kg/min versus 1,212 +/- 172 ml/ kg/min); (V) over dot E in response to 8% CO2 (1,233 +/- 172 ml/kg/min versus 1,565 +/- 327 ml/kg /min); and (V) over dot 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 ) over dot E or (V) over dot O-2peak in obese rats retested at 16 wk of age . Thus, endogenous opioids modulate resting ventilation, ventilatory respon siveness to CO2, and (V) over dot O-2peak in young obese rats by acting spe cifically on receptors located within the central nervous system. This modu lation disappears once the animals reach 16 wk of age.