dibutyryl-cyclic-gmp and Hyperventilation

We investigated the release of surfactant-type phospholipids (S) using the isolated perfused rat lung (IPL). Following a 20 min equilibration period the lungs were hyperventilated for up to 15 min and then lavaged. Changing the peak inspired pressure (PIP) from 10 to 20 cm H2O rapidly increased the rate of release of S; this rate declined after 2 min. In contrast, doubling frequency of ventilation while maintaining the control tidal volume had no effect. The increase in alveolar S reflected release. rather than redistribution, and after 2 min amounted to about 8% of total S in lung tissue. Equivalent hyperventilation in an open-chested intact rat released significantly less S, suggesting possible tonic neurohumoral suppression in vivo. The release of S in the IPL was depressed by reducing temperature, but was not affected by hypoxia, 2,4 dinitrophenol, phenylephrine or dibutyrylguanosine 3',5'-cyclic monophosphate. We suggest that increasing tidal volume may directly distort the alveolar type II cell; each cell reacts to its own threshold distortion by releasing a pool of S in all-or-none fashion.

Topics: Animals; Calcium; Dibutyryl Cyclic GMP; Hyperventilation; Lung; Perfusion; Phenylephrine; Pulmonary Alveoli; Pulmonary Surfactants; Rats; Ventilators, Mechanical

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.

Topics: Albuterol; Animals; Atropine; Bucladesine; Cyproheptadine; Dibutyryl Cyclic GMP; Hyperventilation; Indomethacin; Lung; Male; Perfusion; Phospholipids; Pilocarpine; Pulmonary Surfactants; Rats; Respiration; Tetrodotoxin; Theophylline

Ventilation of rats at high inspiratory pressures raises lung tissue content of guanosine 3',5'-cyclic monophosphate (cGMP). Hyperventilation in rabbits augments release of phospholipid into lavage fluid. Can cGMP, in the absence of hyperventilation, increase lung phospholipid release? Sprague-Dawley rats are injected with [14C]palmitate, and after 1.5 h are anesthetized and ventilated for 20 min. Three groups are ventilated at peak inspiratory pressures (PIP) of 10 cmH2O, while saline, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), or dibutyryl cGMP (DBcGMP) is infused into the pulmonary artery. In a fourth group, saline is infused into the pulmonary artery, but ventilation is performed with PIP of 25 cmH2O. Lung tissue and lavage fluid are then analyzed for phospholipid (PL) content and for incorporation of [14C]palmitate into lavage and tissue PL fractions. Ventilation at increased pressure and infusion of DBcGMP are associated with increases in release of labeled PL into lavage fraction. The findings suggest that the increase in lavage PL release associated with hyperventilation is, at least in part, mediated by cGMP.

Topics: Animals; Bucladesine; Cyclic GMP; Dibutyryl Cyclic GMP; Hyperventilation; Lung; Male; Phospholipids; Rats; Time Factors