Endothelial cell nitric oxide production in acute chest syndrome

Acute chest syndrome (ACS) is the most common form of acute pulmonary disea se associated with sickle cell disease. To investigate the possibility that alterations in endothelial cell(EC) production and metabolism of nitric ox ide (NO) products might be contributory, we measured NO products from cultu red pulmonary EC exposed to red blood cells and/or plasma from sickle cell patients during crisis. Exposure to plasma from patients with ACS caused a 5- to 10-fold increase in S-nitrosothiol (RSNO) and a 7- to 14-fold increas e in total nitrogen oxide (NO,) production by both pulmonary arterial and m icrovascular EC. Increases occurred within 2 h of exposure to plasma in a c oncentration-dependent manner and were associated with increases in endothe lial nitric oxide synthase (eNOS) protein and eNOS enzymatic activity, but not with changes in nitric oxide synthase (NOS) III or NOS II transcripts, inducible NOS (iNOS) protein nor iNOS enzymatic activity. RSNO and NO, incr eased whether plasma was obtained from patients with ACS or other forms of vasoocclusive crisis. Furthermore, an oxidative state occurred and oxidativ e metabolites of NO, particularly peroxynitrite, were produced. These findi ngs suggest that altered NO production and metabolism to damaging oxidative molecules contribute to the pathogenesis of ACS.