TY - JOUR
T1 - Pulmonary resistance and compliance changes evoked by pulmonary opiate receptor stimulation
AU - Willette, Robert N.
AU - Barcas, Peter P.
AU - Krieger, Abbott J.
AU - Sapru, Hreday N.
N1 - Funding Information:
This work was supported by the following grants: East Orange Veterans Administration Center, N.I.H. (HL24347), N.I.H. Biomedical Research support (RR05393), and American Heart Association (N J). The authors would like to thank Dr. George A. Condouris for his generous gift of morphine sulfate, Dr. Joseph Boyle for his valuable discussion of this work and Ms. Tracey J. Lott for her help in preparing this manuscript.
PY - 1983/7/22
Y1 - 1983/7/22
N2 - The administration of [D-Ala2, Met5]enkephalinamide (DAME, 10-250 gmg/kg) or morphine sulfate (MS, 2 mg/kg) into the right atrium (RA) of spontaneously breathing decerebrate rats caused an increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn). The maximal percentage increase in RL for DAME (250 μg/kg) and MS (2 mg/kg) was 120 ± 21 and 160 ± 40%, respectively, occurring during the first 30 s following an initial period of apnea, and subsiding within 1.5-2.0 min. The fall in Cdyn (DAME = -31 ± 8%; MS = -35 ± 4%) followed a more prolonged time course returning to control within 4-5 min. These responses were completely abolished by pretreatment with naloxone HCl (100 μg/kg i.v.), as well as bilateral cervical vagotomy. Pretreatment with antihistaminic, antiserotinergic, and antimuscarinic agents had no effect on the opioid induced changes in RL and Cdyn. Further studies carried out in ventilated animals showed blockade of the mechanical responses following the administration of neuromuscular blockers, C7 spinal cord transection, and ventral midline opening and retraction of the chest. Electromyograms obtained from intercostal muscles showed excitation of expiratory motor units and inhibition of inspiratory motor units following the administration of opioids. Similar results were obtained with phenyldiguanide (PDG), a known stimulant of pulmonary J-receptors. However, PDG effects were not blocked by naloxone. It was concluded that changes in RL resulted from a decrease in thoracic volume and resultant decrease in the radial traction of the airways. Changes in Cdyn were caused by spasm of expiratory muscles of the chest wall.
AB - The administration of [D-Ala2, Met5]enkephalinamide (DAME, 10-250 gmg/kg) or morphine sulfate (MS, 2 mg/kg) into the right atrium (RA) of spontaneously breathing decerebrate rats caused an increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn). The maximal percentage increase in RL for DAME (250 μg/kg) and MS (2 mg/kg) was 120 ± 21 and 160 ± 40%, respectively, occurring during the first 30 s following an initial period of apnea, and subsiding within 1.5-2.0 min. The fall in Cdyn (DAME = -31 ± 8%; MS = -35 ± 4%) followed a more prolonged time course returning to control within 4-5 min. These responses were completely abolished by pretreatment with naloxone HCl (100 μg/kg i.v.), as well as bilateral cervical vagotomy. Pretreatment with antihistaminic, antiserotinergic, and antimuscarinic agents had no effect on the opioid induced changes in RL and Cdyn. Further studies carried out in ventilated animals showed blockade of the mechanical responses following the administration of neuromuscular blockers, C7 spinal cord transection, and ventral midline opening and retraction of the chest. Electromyograms obtained from intercostal muscles showed excitation of expiratory motor units and inhibition of inspiratory motor units following the administration of opioids. Similar results were obtained with phenyldiguanide (PDG), a known stimulant of pulmonary J-receptors. However, PDG effects were not blocked by naloxone. It was concluded that changes in RL resulted from a decrease in thoracic volume and resultant decrease in the radial traction of the airways. Changes in Cdyn were caused by spasm of expiratory muscles of the chest wall.
KW - Enkephalins
KW - Opioids
KW - Pulmonary mechanics
KW - Pulmonary opiate receptors
KW - type J-receptors Pulmonary chemoreflex
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U2 - 10.1016/0014-2999(83)90463-6
DO - 10.1016/0014-2999(83)90463-6
M3 - Article
C2 - 6311577
AN - SCOPUS:0020591922
SN - 0014-2999
VL - 91
SP - 181
EP - 188
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -