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.

Time course for inhibition of lipopolysaccharide-induced lung injury by genistein: Relationship to alteration in nuclear factor-κB activity and inflammatory agents*

“…Inducible NO synthase expression in macrophages caused by LPS or interleukin-1 involves the activation of tyrosine kinases as well as the activation of NF-B (32). LPS-induced overproduction of NO due to induction of inducible NO synthase has been shown to contribute to lung injury (33,34) as well as liver injury and dysfunction (26). Accordingly, we demonstrate here that the multiple dosing schedule with genistein significantly suppressed LPS-induced NF-B activation as well as MMP-9 activity and NO production at 24 hrs after LPS treatment, whereas a single dose of genistein did not.…”

Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury

“…One 0.5-ml aliquot of each urine sample was used to measure NO. The urine aliquots were heated at 90ЊC in an acidic environment (1 M HCl) in the presence of vanadium (III) chloride to catalyze the reduction of NO 3 Ϫ to NO 2 Ϫ and then to NO (20)(21)(22)(23)(24)(25)(26). NO levels were measured with a chemiluminescent analyzer (Sievers Nitric Oxide Analyzer, model 280i; Sievers, Boulder, CO).…”

Hyperbaric oxygen attenuates lipopolysaccharide-induced acute lung injury

“…Evidence has shown that NO in high concentrations may cause lung injury [29,30] either by itself or by the formation of peroxynitrite which is a highly active radical [31]. Others have shown that inhibition of NO synthesis by L-NAME enhanced LPS-induced acute lung injury [32].…”