Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 1009-1015

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

S. D. LEE, H. NAKANO, L. E. GOSSELIN, J. A. KRASNEY, E. H. SCHLENKER, and G. A. FARKAS

Departments of Physical Therapy, Exercise and Nutrition Sciences, and Physiology and Biophysics, University at Buffalo, Buffalo, New York; and Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota

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 ( E) at rest and during hypercapnic challenges, as well as peak oxygen consumption ( 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 E and O_2peak. Similarly, N_M failed to alter E and 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 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); E in response to 8% CO₂ (1,233 ± 172 ml/kg/min versus 1,565 ± 327 ml/kg/min); and 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 E or O_2peak in obese rats retested at 16 wk of age. Thus, endogenous opioids modulate resting ventilation, ventilatory responsiveness to CO₂, and 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.

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