n-methylnaloxone and Hypoxia

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

Topics: Animals; Carbon Dioxide; Hypoxia; Kinetics; Male; Naloxone; Narcotic Antagonists; Obesity, Morbid; Opioid Peptides; Oxygen; Pulmonary Gas Exchange; Pulmonary Ventilation; Quaternary Ammonium Compounds; Random Allocation; Rats; Rats, Zucker

Endogenous opioids are known to inhibit chemoreception and ventilatory control. The opioid antagonist naloxone stimulates ventilation by removing this inhibition. To study whether the effects of opiate receptor antagonism are mediated by a central or a peripheral mechanism, we administered equal doses of naloxone hydrochloride (NHCl, an agent that crosses the blood-brain barrier) and naloxone methiodide (NM, an agent that does not cross the blood-brain barrier) to awake golden Syrian hamsters. Both naloxone preparations significantly increased the oxygen consumption (46% for NHCl and 90% for NM) in these animals relative to saline. Naloxone hydrochloride, but not NM, stimulated ventilation (30%) and tidal volume (34%) when the animal was subjected to a hypercapnic challenge, predominantly sensed in the brain. In contrast, both naloxones stimulated ventilation by 52% compared to saline treatment when the hamsters were exposed to a hypoxic challenge, predominantly sensed peripherally. These results suggest that endogenous opioids modulate both central and peripheral chemoreception in the hamster.

Topics: Animals; Cricetinae; Hypoxia; Injections, Subcutaneous; Male; Mesocricetus; Naloxone; Oxygen Consumption; Quaternary Ammonium Compounds; Respiratory Mechanics; Tidal Volume