Inhaled nitric oxide reduces tyrosine nitration after lipopolysaccharide instillation into lungs of rats

Nitric oxide (NO) may either protect against or contribute to inflammatory lung injury. In this study we investigated whether inhalation of 20 ppm NO alters tyrosine nitration, and we assessed the degree of lung inflammation and edema in rats after lipopolysaccharide (LPS) instillation. The amount o f nitrotyrosine relative to the total amount of tyrosine was measured in lu ng homogenates, and lung tissue sections were stained for nitrotyrosine and aminotyrosine (a reduced form of nitrotyrosine). Leukocytes in bronchoalve olar lavage fluid (BALF) were counted, and myeloperoxidase activity was mea sured in lung homogenate. Lung edema and inflammatory cell accumulation in lung tissue were estimated by extravascular lung water weight (EVLW) and ex travascular dry lung weight (EVDW), respectively. LPS instillation caused i ncreases in nitrotyrosine concentration and immunohistochemical staining of nitrotyrosine and aminotyrosine in the lungs, LPS instillation increased t he BALF leukocyte count, myeloperoxidase activity in lung tissue, and both EVLW and EVDW. Inhalational exposure to 20 ppm NO induced nitrotyrosine and aminotyrosine formation only in bronchial epithelial cell surface of the l ungs not instilled with LPS. NO inhalation reduced the increases in nitroty rosine and aminotyrosine in LPS-instilled lung tissue as well as the leukoc yte count in BALF and myeloperoxidase activity in lung tissue, but it did n ot significantly change EVLW or EVDW. Leukocyte depletion in LPS-instilled rats reduced interstitial inflammatory cells, which were stained with nitro tyrosine and aminotyrosine, and attenuated the nitrotyrosine staining of al veolar capillaries. These results suggest that inhalation of 20 ppm NO redu ces leukocyte accumulation in the lungs and inhibits tyrosine nitration cau sed by LPS instillation.