Journal of Applied Physiology, Vol 72, Issue 2 590-596, Copyright © 1992 by American Physiological Society

ARTICLES

Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading

J. J. Petrozzino, A. T. Scardella, T. V. Santiago and N. H. Edelman
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.

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.

This article has been cited by other articles:

				S. Zakynthinos, P. Katsaounou, M.-H. Karatza, C. Roussos, and T. Vassilakopoulos Antioxidants Increase the Ventilatory Response to Hyperoxic Hypercapnia Am. J. Respir. Crit. Care Med., January 1, 2007; 175(1): 62 - 68. [Abstract] [Full Text] [PDF]

				T. Vassilakopoulos, C. Roussos, and S. Zakynthinos The immune response to resistive breathing Eur. Respir. J., December 1, 2004; 24(6): 1033 - 1043. [Abstract] [Full Text] [PDF]

				C. Roussos and A. Koutsoukou Respiratory failure Eur. Respir. J., November 16, 2003; 22(47_suppl): 3s - 14s. [Abstract] [Full Text] [PDF]

				H. V. Forster Plasticity in Respiratory Motor Control: Invited Review: Plasticity in the control of breathing following sensory denervation J Appl Physiol, February 1, 2003; 94(2): 784 - 794. [Abstract] [Full Text] [PDF]

				ATS/ERS Statement on Respiratory Muscle Testing Am. J. Respir. Crit. Care Med., August 15, 2002; 166(4): 518 - 624. [Full Text] [PDF]

				T. Vassilakopoulos, S. Zakynthinos, and C. Roussos Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R1013 - R1019. [Abstract] [Full Text] [PDF]

				H. E. Greenberg, R. S. Rao, A. L. Sica, and S. M. Scharf Effect of chronic resistive loading on hypoxic ventilatory responsiveness J Appl Physiol, February 1, 1997; 82(2): 500 - 507. [Abstract] [Full Text] [PDF]