Catalase pretreatment attenuates oleic acid-induced edema in isolated rabbit lung.
Because reactive O2 metabolites have been demonstrated to be potent mediators of vascular dysfunction and are synthesized by lung tissue, their involvement as mediators of oleic acid (OA)-induced pulmonary edema in the isolated Krebs-perfused rabbit lung was assessed. Injection of OA (0.1 ml) into the pulmonary artery after vehicle pretreatment induced marked increases in lung weight [50.4 +/- 13.9 vs. 4.2 +/- 2.0 (SE) g 45 min after OA or vehicle, respectively, P less than 0.05], an index of pulmonary edema, and airway pressure. OA also caused a significant though minimal increase in pulmonary arterial pressure. Pretreatment with catalase (1,000 U/ml), a scavenger of H2O2, significantly (P less than 0.05, Friedman's) attenuated the increases in lung weight (50.4 +/- 13.9 vs. 15.1 +/- 4.9 g), airway pressure, and pulmonary arterial pressure. In contrast to catalase, pretreatment with Cu-tryptophan (40 microM), a lipid-soluble scavenger of superoxide, provided no protective effect by itself, nor was there any potentiation of protection when combined with catalase. Further evidence implicating O2 metabolites in OA-induced edema was obtained by electron paramagnetic resonance (EPR) spectroscopy of perfusate samples to which the spin trap, sodium 3,5-dibromo-4-nitrosobenzenesulfonate (10 mM), was added. Analysis of these samples revealed the presence of free radicals after OA. Pretreatment with catalase (1,000 U/ml) and superoxide dismutase (250 U/ml) attenuated the EPR signal, indicating that proximal formation of O2 free radicals was in part responsible for the signal. These results suggest that reactive O2 metabolites are mediators of OA-induced pulmonary edema in the isolated perfused rabbit lung.
Katz
S A
SA
Department of Physiology, Medical University of South Carolina, Charleston 29425.
Venkatachalam
M
M
Crouch
R K
RK
Heffner
J E
JE
Halushka
P V
PV
Wise
W C
WC
Cook
J A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology*; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000009:adverse effects*; D010100:Oxygen / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011817:Rabbits
D005609:Free Radicals; D009829:Oleic Acids; D019301:Oleic Acid; D002374:Catalase; D010100:Oxygen