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

We used the isolated rat lung to investigate surfactant release. The lung was ventilated at 60.min^-1 with 5% CO₂-95% O₂ and perfused at 10 ml.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 cmH₂O produced progressively greater phospholipid (PL) yields. Whereas ventilating with PIP of 9 cmH₂O and end-expired pressure (EEP) of 5 cmH₂O produced 5.9 ± 0.8 (mean ± SD) (n = 17) mg PL.g dry lung^-1, ventilating with PIP of 20 cmH₂O and EEP of 0 cmH₂O 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 adenosine 3',5'-cyclic monophosphate but not by pilocarpine or dibutyryl guanosine 3',5'-cyclic monophosphate. Theophylline potentiated release with mild hyperventilation. We conclude, that 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.