Selective action of prostaglandin F 2α during paraquat-induced pulmonary edema in the perfused lung

Abstract

Lung prostaglandins (PGs) play a key role in normal pulmonary vascular regulation. We investigated PG metabolism during edema formation following paraquat-induced damage with an isolated perfused rat lung preparation. Lungs perfused with paraquat (PQ), 1 × 10 −7 m to 1 × 10 −2 m, showed significant increases in PGF 2α prior to detectable functional and pathological changes (increases in airway resistance, vascular resistance, and edema). No changes in PGE were observed. PGF 2α in perfused lungs showed a dose-related response following PQ exposure (up to 300% increase over control values). Lungs perfused with PQ and ventilated with high oxygen (95% O 2–5% CO 2) instead of air-5% CO 2 showed a dramatic potentiation in the selective increase of PGF 2α, with levels reaching over 1 ng/ml (a 2600% increase over control values). The addition of exogenous PGF 2α to the perfusate without PQ initiated edema in a dose-related fashion, indicating the potential of PGF 2α as a causative agent in lung edema formation from PQ injury. The addition of ibuprofen (a nonsteroidal anti-inflammatory agent) to the perfusion medium blocked endogenous release of PGF 2α in lungs perfused with PQ and prevented the onset of edema, providing further evidence that PGF 2α is linked to oxidant-induced edema. These data show that in the perfused lung: (1) PQ caused a selective increase of PGF 2α; (2) this selective increase occurred prior to the onset of edema; (3) exogenous PGF 2α alone induced pulmonary edema; and (4) ibuprofen, in doses which blocked PGF 2α, also prevented edema formation.