CONTROL OF LUNG SURFACTANT BY VENTILATION, ADRENERGIC MEDIATORS, AND PROSTAGLANDINS IN RABBIT

Abstract

Increasing minute ventilation (.ovrhdot.VE) in rabbit lung by adding a dead space previously was shown to augment pulmonary surfactant in the airspaces by a cholinergically mediated mechanism. Using the same model, increasing .ovrhdot.VE augmented airspace phospholipid, the main component of surfactant, from 2.50 .+-. 0.61 (mean .+-. SD) mg/g of lung during normal .ovrhdot.VE to 3.15 .+-. 1.22 (mean .+-. SD) mg/g of lung during increased .ovrhdot.VE (P = 0.02). Both blocking .beta.-adrenergic receptors with propranolol or sotalol and inhibiting prostaglandin synthetase with indomethacin or sodium meclofenamate prevented the expected increase in phospholipid during increased .ovrhdot.VE (P < 0.05). The .beta.-2 agonist, terbutaline, increased phospholipid by 43% during normal .ovrhdot.VE (P < 0.01), and propranolol blocked this increase (P < 0.05). Isoproterenol, arachidonic acid, prostaglandins [PG] E1, E2, F2.alpha. and a cyclic endoperoxide analog of PGH2 (U-46619) injected during normal .ovrhdot.VE failed to increase phospholipid. Acetylcholine .beta.-surfactant during increased .ovrhdot.VE.