Effect of Oxotremorine and Epinephrine on Lung Surfactant Secretion in Neonatal Rabbits

Abstract
Summary: The phosphatidylcholine (PC) content (mg/g dry lung weight; mean ± S.E.) of lung washes of 1 to 3-day-old rabbits was significantly greater 30 min after the injection of the muscarinic agonist oxotremorine (0.2 mg/kg; 50.5 ± 2.9 mg/g; 2 P < 0.01) or epinephrine (50 μg/kg; 78.0 ± 14.8 mg/g; 2 P < 0.001) than saline (25.7 ±1.9 mg/g). Injection of atropine (2 mg/kg), dl-propranolol (1 mg/kg) but not d-propranolol (1 mg/kg) at 40 min or adrenalectomy at 45 min before killing abolished the increase produced by oxotremorine (2 P < 0.001). Also, dl-propranolol antagonized the increase produced by epinephrine. Palmitic and myristic acids were the major fatty acids in the lung wash PC of control and oxotremorine-treated rabbits. The residual lung tissue PC content following atropine (2 mg/kg; 104.4 ± 18.5 mg/g) was significantly greater (2 P < 0.05) than following saline (72.6 ± 6.0 mg/g) but not different (2 P < 0.05) in other treatment groups. The total lung content of PC was 55% greater (2 P < 0.001) than controls 30 min after epinephrine (50 μg/kg). The surface activity of lung washes (mg/g dry lung weight; mean ± S.E.), assayed on a surface tension balance using dipalmitoyl-phosphatidylcholine as standard, was significantly greater (2 P < 0.05) 30 min following injection of oxotremorine (0.2 mg/kg; 73.8 ± 9.9 mg/g) or epinephrine (50 μg/kg; 72.2 ± 10.2 mg/g) than saline (42.8 ± 2.0 mg/g). Ten-min infusions of oxotremorine (0.34 μg/ml) into isolated, ventilated, perfused neonatal rabbit lung preparations failed to alter the PC content of the subsequent wash, but this was significantly (2 P < 0.05) raised from 3.7 (± 0.8) to 4.8 (± 0.8) mg/g dry lung wt by a 10 min infusion of epinephrine (3.4 μg/ml). Speculation: Alteration of the rate of secretion of lung surfactant into alveoli may control the rate of biosynthesis. Disorders of lung surfactant secretion may be involved in the pathogenesis of respiratory distress syndrome.