Opioidergic modulation of ventilatory response to sustained hypoxia in obese Zucker rats.
OBJECTIVE
To determine whether altered central and/or peripheral opioidergic mechanisms contribute to the altered ventilatory response to sustained hypoxia in obese Zucker rats.


METHODS
Eight lean (176 +/- 8 [SEM] g) and eight obese (225 +/- 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary ventilation ((E)), tidal volume (V(T)), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O(2)) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (N(M); 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (N(HCl); 5 mg/kg, peripheral and central opioid antagonist).


RESULTS
Administration of N(M) and N(HCl) in lean animals had no effect on (E) either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, N(M) failed to alter (E) in obese rats. In contrast, N(HCl) significantly (p < 0.05) increased (E) and V(T) both at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, V(T) remained elevated with N(HCl), but the earlier elevation of (E) seemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia.


CONCLUSIONS
Thus, endogenous opioids modulate both resting (E) and 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.
Lee
S D
SD
Department of Physical Therapy, Exercise and Nutrition Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14214-3079, USA.
Magalang
U J
UJ
Krasney
J A
JA
Farkas
G A
GA
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D000860:Hypoxia / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009767:Obesity, Morbid / Q000503:physiopathology*; D018847:Opioid Peptides / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology; D000644:Quaternary Ammonium Compounds; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D000644:Quaternary Ammonium Compounds; D002245:Carbon Dioxide; D009270:Naloxone; C041269:N-methylnaloxone; D010100:Oxygen