The role of intrapulmonary nitric oxide generation in the development of adult respiratory distress syndrome.

Abstract

This study was conducted to investigate the role of nitric oxide (NO) in the development of adult respiratory distress syndrome (ARDS). An experimental model of endotoxemia-induced ARDS was prepared in guinea pigs and the following parameters were measured: pulmonary vascular permeability, the nitrate and nitrite concentrations in blood and bronchoalveolar lavage fluid (BALF), and the activities of constitutive and inducible NO synthase in lung tissue following the administration of lipopolysaccharide (LPS). Following the intravenous administration of 0.5 mg/kg LPS, the pulmonary vascular permeability increased, as did the concentrations of nitrate and nitrite in the BALF and blood. The activities of both constitutive and inducible NO synthase (NOS) increased significantly in the lung tissue 4 h after the intravenous administration of LPS, the constitutive form showing significantly higher activity than the inducible form. Furthermore, the increase of vascular permeability in the lungs after LPS injection was blocked by the subcutaneous administration of N(G)-monomethyl-l-arginine. These observations indicate that the intrapulmonary generation of NO may play an important role in the development of ARDS.