ENDOGENOUS OPIOIDS MODULATE VENTILATION IN THE OBESE ZUCKER RAT

This study evaluated the modulatory role of endogenous opioids on vent ilation in young and mature, lean and obese male Zucker rats. Naloxone , an opioid receptor antagonist, and saline (control) were administere d subcutaneously to awake rats, and ventilation in air and in response to an hypoxic and an hypercapnic gas challenge measured. In response to naloxone young,obese but not lean rats exhibited a marked increase of ventilation in all three conditions. Older obese Zucker rats that w ere morbidly obese breathed at a frequency of over 200 breaths per min ute and showed only a modest increase of ventilation in response to na loxone. Older lean rats increased ventilation with naloxone only when exposed to hypercapnia. Unlike the stimulatory effects hypoxia and hyp ercapnia had on ventilation in older, lean rats, the ventilatory respo nses of the obese, older rats to hypoxia and to hypercapnia were blunt ed. We conclude that the obese Zucker rat may be a good animal model t o assess how chest wall loading and endogenous opioids interact in the development of ventilatory control abnormalities.