Pulmonary opiate receptor activation evokes a cardiorespiratory reflex

Abstract

The administration of [D-Ala 2,Met 5]enkephalinamide (D-AME) and [D-Ala 2,Leu 5]enkephalinamide (D-ALE) into the right atrium of decerebrate rats caused bradycardia, a slight transient biphasic blood pressure response and apnea within 1–2 sec. Apnea was followed by rapid shallow breathing. These effects were dose related (1–1000 μg/kg) and blocked by pretreatment with naloxone. Atropine blocked the bradycardia. Sectioning the vagi at the level of the diaphragm did not affect the responses, whereas bivagotomy below the cardiac branches abolished all responses. The triad of responses was attributed to a reflex action arising from vagal afferents within the lung. These results were confirmed in paralyzed, artificially ventilated animals. In these animals, the enkephalin analogues produced a cessation of phrenic nerve (PN) activity followed by a decrease in the duration of bursts. The recurrent laryngeal nerve (RLN) was concomitantly excited in a continuous decremental fashion. This excitation was independent of PN inhibition. Recordings of single and near single pulmonary vagal affarents demonstrated no effect of D-AME or D-ALE on stretch and irritant receptors. However, type J-receptors were stimulated.