Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease

Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteri opathy (PPA), a specific pulmonary Vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proli feration. Increased local production of NO has been suggested in this condi tion. Because reported data on the expression of endothelial NO-synthase (e cNOS) have been contradictory, we speculated that the expression of the ind ucible isoform of NOS (iNOS) is enhanced in this form of pulmonary hyperten sion. We investigated immunohistochemically the expression of ecNOS and iNO S in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulm onary blood flow but normal pulmonary artery pressure (n = 10), with conges tive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity fo r ecNOS and iNOS was present both in normal and diseased pulmonary arteries . Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of i mmunoreactivity, both for ecNOS and iNOS, showed no correlation with the se verity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively ). In contrast to ecNOS, immunoreactivity for iNOS was increased in patient s with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific p ulmonary arteriopathy.