Endogenous opioid modulation of hypercapnic-stimulated respiration in the rat.
The role of endogenous opioids in respiratory control in the pentobarbital anaesthetised rat was investigated using a rebreathing technique to generate a progressively increasing hypercapnic stimulus to the respiratory centers following administration of an opioid antagonist or agonist. Respiratory output was measured by intraesophageal pressure (IEP) changes, and a ventilatory equivalent (VEq) was calculated by multiplying IEP by respiratory rate (mmHg.min-1). A non-selective opioid antagonist, naloxone (0.4 mg/kg i.v.), significantly enhanced the slope of the CO2 response curve for VEq (20 +/- 3 mmHg.min-1.%CO2-1) compared with the control (14 +/- 2 mmHg.min-1.%CO2(-1)) (P < 0.05; n = 14). A similar enhancement of the hypercapnic response by naloxone was found in rats anaesthetised with urethane (n = 5). The mu receptor agonist dermorphin (1 mg/kg i.v.) significantly depressed the slope of the CO2 response curve for IEP (-0.01 +/- 0.03) compared with the control (0.10 +/- 0.03) in pentobarbital anaesthetised rats (P < 0.05; n = 5) but had no significant effect on respiratory rate. These results suggest a role of endogenous opioids in the modulation of respiration during hypercapnia.
Eager
K R
KR
School of Biological Sciences, Victoria University of Wellington, New Zealand.
Robinson
B J
BJ
Galletly
D C
DC
Miller
J H
JH
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D006935:Hypercapnia / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000032:analysis / Q000494:pharmacology; D018847:Opioid Peptides; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D014520:Urethane / Q000494:pharmacology
D000701:Analgesics, Opioid; D009294:Narcotics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D009270:Naloxone; D014520:Urethane; D010100:Oxygen