Effect of nitrite on endothelial function in isolated lung

Nitrated tyrosine, implicated in protein dysfunction, is increased in vario us tissues in association with diverse pathological processes. Angiotensin converting enzyme (ACE) is a luminal vascular endothelial enzyme whose dysf unction is an early sign of endothelial injury. ACE contains a tyrosine cri tical for its enzymatic activity. Others have shown that nitrite exacerbate s the ACE dysfunction of cultured endothelial cells in contact with activat ed polymorphonuclear neutrophils (PMN). We hypothesized that exogenous nitr ite would enhance endothelial ACE dysfunction associated with PMN activatio n in the isolated lung. Rats received lipopolysaccharide (LPS) 2 h prior to isolated lung per-fusion with Ficoll containing buffer. Either formyl-Met- Leu-Phe (fMLP, 10(-7) M) or phorbol myristate acetate (PMA, 10(-7) M) was u sed to activate PMN in lungs treated or not treated with 300-muM nitrite. A first pass indicator dilution method and first order reaction kinetics wer e used to determine ACE activity, while lung Ficoll content served as an in dex of vascular permeability. Both fMLP and PMA decreased endothelial ACE a ctivity and increased pulmonary artery pressure, edema and vascular permeab ility. Exogenous nitrate did not potentiate the decrease in ACE activity, t he lung injury or nitrotyrosine immunoreactivity of lung homogenates. In co ntrast to observations in cultured endothelial cells, our findings in the w hole lung are compatible with the speculation of others that the rat lung h as an unidentified factor, which minimizes accumulation of nitrated protein s. (C) 2001 Elsevier Science Inc. All rights reserved.