The Role of Endogenous Opioids in the Ventilatory Response to Sustained Respiratory Loads
The potent respiratory depressant effects of exogenous opiates are well known. Morphine and other opiates reduce ventilation, the ventilatory responses to hypercapnia and hypoxia, as well as the respiratory compensation for an acute increase in airway resistance.1-3 The discovery of endogenous opioid peptides such as beta-endorphin and enkephalin led to investigations into the possible role of these peptides in ventilatory control in humans. In one such study Santiago and co-workers found that the opioid antagonist naloxone restored the respiratory compensation for a flow-resistive load in those patients with chronic obstructive pulmonary disease in whom it was found to be absent.4 They postulated that in these patients endogenous opioids were elaborated in response to the stress of chronically increased airway resistance resulting in attenuation of compensation for the flow-resistive load. In a subsequent study in an unanesthetized goat model we tested the hypothesis that shorter periods of stress produced by increased airway resistance would activate the endogenous opioid system and reduce the subsequent ventilatory response.5 We found in animals exposed to two and one-half hours of inspiratory flow-resistive loading that the reduction in tidal volume was partially reversed by naloxone given at the conclusion of the loading period and that levels of immunoreactive beta-endorphin measured in the cisternal cerebrospinal fluid were increased. Our subsequent studies have been directed at defining the effect of activation of the endogenous opioid system on central respiratory output to the respiratory muscles and the peripheral signal responsible for the activation of this system. The results of these studies are discussed in detail below.
KeywordsTidal Volume Respiratory Muscle Ventilatory Response Endogenous Opioid Endogenous Opioid System
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- 6.A.T. Scardella, T.V. Santiago, and N.H. Edelman, Naloxone alters the early response to an inspiratory flow-resistive load, J. Appl. Physiol. 67:1141 (1989).Google Scholar