Selective action of prostaglandin F2 alpha during paraquat-induced pulmonary edema in the perfused lung.
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 X 10(-7) M to 1 X 10(-2) M, showed significant increases in PGF2 alpha prior to detectable functional and pathological changes (increases in airway resistance, vascular resistance, and edema). No changes in PGE were observed. PGF2 alpha 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% O2-5% CO2) instead of air-5% CO2 showed a dramatic potentiation in the selective increase of PGF2 alpha, with levels reaching over 1 ng/ml (a 2600% increase over control values). The addition of exogenous PGF2 alpha to the perfusate without PQ initiated edema in a dose-related fashion, indicating the potential of PGF2 alpha 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 PGF2 alpha in lungs linked to oxidant-induced edema. These data show that in the perfused lung: (1) PQ caused a selective increase of PGF2 alpha; (2) this selective increase occurred prior to the onset of edema; (3) exogenous PGF2 alpha alone induced pulmonary edema; and (4) ibuprofen, in doses which blocked PGF2 alpha, also prevented edema formation.
D000818:Animals; D015237:Dinoprost; D007052:Ibuprofen / Q000494:pharmacology; D008168:Lung / Q000032:analysis; D008297:Male; D010269:Paraquat / Q000633:toxicity*; D010477:Perfusion; D011460:Prostaglandins F / Q000032:analysis / Q000502:physiology*; D011654:Pulmonary Edema / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains
D011460:Prostaglandins F; D015237:Dinoprost; D010269:Paraquat; D007052:Ibuprofen