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Nitrated tyrosine, implicated in protein dysfunction, is increased in various tissues in association with diverse pathological processes. Angiotensin converting enzyme (ACE) is a luminal vascular endothelial enzyme whose dysfunction is an early sign of endothelial injury. ACE contains a tyrosine critical for its enzymatic activity. Others have shown that nitrite exacerbates the ACE dysfunction of cultured endothelial cells in contact with activated polymorphonuclear neutrophils (PMN). We hypothesized that exogenous nitrite would enhance endothelial ACE dysfunction associated with PMN activation in the isolated lung. Rats received lipopolysaccharide (LPS) 2 h prior to isolated lung perfusion with Ficoll containing buffer. Either formyl-Met-Leu-Phe (fMLP, 10(-7) M) or phorbol myristate acetate (PMA, 10(-7) M) was used to activate PMN in lungs treated or not treated with 300-microM nitrite. A first pass indicator dilution method and first order reaction kinetics were used to determine ACE activity, while lung Ficoll content served as an index of vascular permeability. Both fMLP and PMA decreased endothelial ACE activity and increased pulmonary artery pressure, edema and vascular permeability. Exogenous nitrate did not potentiate the decrease in ACE activity, the lung injury or nitrotyrosine immunoreactivity of lung homogenates. In contrast to observations in cultured endothelial cells, our findings in the whole lung are compatible with the speculation of others that the rat lung has an unidentified factor, which minimizes accumulation of nitrated proteins.

Type

Journal article

Journal

Gen Pharmacol

Publication Date

06/2000

Volume

34

Pages

401 - 408

Keywords

Animals, Blood Pressure, Capillary Permeability, Carcinogens, Dimethyl Sulfoxide, Endothelium, Vascular, Free Radical Scavengers, Lipopolysaccharides, Lung, Male, Models, Animal, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Nitrites, Peptidyl-Dipeptidase A, Rats, Rats, Wistar, Respiratory Distress Syndrome, Adult, Tetradecanoylphorbol Acetate, Tyrosine