Control of release of surfactant phospholipids in the isolated perfused rat lung

Abstract

The isolated rat lung was used to investigate surfactant release. The lung was ventilated at 60 .cntdot. min-1 with 5% CO2-95% O2 and perfused at 10 ml .cntdot. min-1 with Krebs-bicarbonate (4.5% albumin). After 20 min during which antagonist drugs were present, the lungs were either hyperventilated or agonist drugs were added. After another 15 min lungs were lavaged. Peak inspired pressures (PIP) in excess of 12 cm H2O produced progressively greater phospholipid (PL) yields. Whereas ventilating with PIP of 9 cm H2O and end-expired pressure (EEP) of 5 cm H2O produced 5.9 .+-. 0.8 (mean .+-. SD) (n = 17) mg PL .cntdot. g dry lung-1, ventilating with PIP of 20 cm H2O and EEP of 0 cm H2O produced 10.1 .+-. 1.3 (n = 26). PL release was unaffected by tetrodotoxin, propranolol, atropine, cyproheptadine or indomethacin. PL was increased by salbutamol and dibutyryl cAMP but not by pilocarpine or dibutyryl cGMP. Theophylline potentiated release with mild hyperventilation. Increasing tidal volume immediately releases surfactant, probably by distorting the type II cell and elevating cAMP. An intrapulmonary neural reflex is not involved in this response of the isolated rat lung, nor is histamine, 5-hydroxytryptamine or a prostaglandin.