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

Abstract

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. 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.

Molecular cloning and expression of leptin in gray and harbor seal blubber, bone marrow, and lung and its potential role in marine mammal respiratory physiology

“…Wyszogrodski et al (55) found that increased ventilation in experimental animal models led to an increased usage of surfactant. Spontaneously breathing rabbits had an increased amount of phospholipid in bronchoalveolar lavages following hyperventilation (34); further in vitro and in vivo studies confirmed that hyperventilation through mechanical distension induces surfactant release (30,53,54). The presence of pulmonary surfactant in excess may be particularly important for seals, which repeatedly dive to forage.…”

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

“…There is extensive experimental evidence to indicate that lung inflation increases the production of surfactant phospholipids in intact animals (7,21,40), isolated organs (7,18,19), and by cells in culture (6,38). For example, Wirtz and Dobbs (38) showed the effect of a single mechanical stretch on TII cell surfactant phospholipid secretion, although surprisingly, the effect was not sustained by subsequent stretches.…”

Surfactant deficiency in rats without a decreased amount of extracellular surfactant.

“…A large inflation or sigh, deaggregates the surfactant that is sedimented at low centrifugal forces thereby increasing the pool of more rapidly adsorbing surfactant (5, 6), which in turn increases the rate at which losses from the surface film may be replaced by surfactant in the hypophase, thereby restoring alveolar stability. This explanation for the corrective action of a large breath does not preclude a contribution of surfactant, newly secreted in response to a large inflation (19)(20)(21)(22)(23)(24), to the improved alveolar stability. However, the amount of surfactant secreted in response to a single large inflation (23) is substantially less than that generated by deaggregation of easily pelleted material (5,6).…”