THE CARDIOVASCULAR AND RESPIRATORY EFFECTS OF ENKEPHALINS: PULMONARY OPIATE RECEPTORS.

摘要

The right atrial administration of enkephalin analogues or morphine sulfate evokes a cardiorespiratory reflex in rats. The cardiorespiratory effects include bradycardia, hypotension, and apnea followed by rapid shallow breathing. These effects of opioids are caused by an initial interaction with pulmonary opiate receptors (a novel population of opiate receptors) and subsequent stimulation of pulmonary vagal afferents; believed to be pulmonary J-fibers. The bradycardia was caused by a reflex activation of vagal cardiomotor neurons. Hypotension was the result of reflex inhibition of vasomotor outflow. Apnea and rapid shallow breathing occurred because of the effects of pulmonary afferent projections to respiratory motoneuron pools. These effects of pulmonary opiate receptor stimulation were apparent in decerebrate as well as conscious rats.;Pulmonary opiate receptor stimulation also caused a large increase in laryngeal resistance to airflow. Single unit recordings showed that the increase in laryngeal resistance was caused by activation and recruitment of expiratory motoneurons and inhibition of inspiratory motoneurons in the recurrent laryngeal nerve.;An investigation of the pulmonary mechanical changes associated with pulmonary opiate receptor activation revealed an opioid induced increase in lung resistance and a decrease in dynamic compliance. The increase in resistance was caused by dynamic compression of the airway and the fall in dynamic compliance was the result of an increase in the chest wall expiratory tone. These results may explain the rigidity often observed following the intravenous administration of opioids in humans.;Opiate receptor autoradiography of the pulmonary branch of the vagus nerve demonstrated the presence of opiate receptors. This observation suggests that pulmonary opiate receptors may be located on vagal afferent nerve endings.;In conclusion, when opioids are administered intravenously, they initially stimulate pulmonary opiate receptors. Therefore, during the first minutes following injection of opiates, e.g. morphine, the peripheral effects (mediated by pulmonary opiate receptors) will mask the more depressant central effects of opiates. These results offer an experimental basis for the acute benefits and rational use of peripherally acting opiate antagonists. If pulmonary opiate receptors exist in human lungs (evidence suggest that they do exist), then an effective peripheral opiate antagonist would prevent their stimulation and possible untoward reflex effects.