Activation of microvascular endothelial cells in active ulcerative colitis and detection of inducible nitric oxide synthase

Endothelial nitric oxide (NO) synthase (NOS) that is expressed constitutively on microvascular endothelium is believed to be essential to systemic and/or local vascular integrity. Endothelial cells (ECs) were reported to express inducible NOS (iNOS) under some conditions iNOS expression indicates vascular activation. In this study we examined microvascular activation using ECs obtained from patients with ulcerative colitis (UC). We cultured ECs from the mesenteries of surgical UC patients and assayed NOS activity by NADPH-diaphorase cytochemistry and immunocytochemistry with an anti-iNOS antibody. Strong NOS activity was demonstrated on the cells from UC patients (5/5), whereas no activity was detected on the cells from cancer patients and human umbilical vein endothelial cells (HUVEC, 0/5, 0/5). Strong iNOS activity was detected by immunoreaction, and large amounts of NO generated were detected by the conversion from [C-14]arginine to [C-14]citrulline (HUVEC 624 +/- 376 vs. EC-UC 1,492 +/- 233 dpm). These results suggest the possibility that ECs express spontaneous and continuous iNOS in active UC. They indicate a close relationship of vascular activation with the pathogenesis of UC.