Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading.
Inspiratory flow-resistive loading (IRL) in unanesthetized goats causes central elaboration of endogenous opioids, which is accompanied by inhibition of several respiratory muscles. The peripheral stimulus responsible for mediating this phenomenon is unknown. We hypothesized that lactic acid mediates release of endogenous opioids during IRL. Unanesthetized goats were pretreated with either saline or dichloroacetate (DCA; 50 mg/kg iv), a blocker of lactic acid formation, and subjected to IRL (50 cmH2O.l-1.s) for 120 min followed by naloxone (NLX; 0.3 mg/kg iv). Electromyographic activities of the diaphragm (EMGdi), external oblique (EMGeo), and external intercostal (EMGei) were measured and expressed as a percentage of activity at an end-tidal CO2 of 8%. DCA blocked the NLX-induced augmentation of all EMGs observed after 120 min of IRL as follows (means +/- SE): delta EMGdi from 20.8 +/- 5.6% (saline) to 1.2 +/- 2.7% (DCA), delta EMGeo from 116.6 +/- 30.9% (saline) to 5.3 +/- 11.4% (DCA), and delta EMGei from 43.8 +/- 11.3% (saline) to -4.5 +/- 5.6% (DCA) (all P less than 0.05, DCA vs. saline). We conclude that lactic acid produced by the contracting respiratory muscles is the stimulus responsible for endogenous opioid pathway activation during IRL.
Petrozzino
J J
JJ
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Scardella
A T
AT
Santiago
T V
TV
Edelman
N H
NH
D000344:Afferent Pathways / Q000502:physiology; D000403:Airway Resistance; D000818:Animals; D002245:Carbon Dioxide; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004723:Endorphins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006041:Goats; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology
D004723:Endorphins; D007773:Lactates; D002245:Carbon Dioxide; D019344:Lactic Acid; D009270:Naloxone; D003999:Dichloroacetic Acid