Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine

The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indometh acin (10 mg kg(-1), s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled L-arginine to citrulli ne) and enhancement of vascular leakage of radiolabelled human serum albumi n in the jejunum which commenced 18 h after indomethacin. Similar effects w ere not observed in the ileum, colon or caecum. In addition, macroscopic le sions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, wherea s both the ileum and colon are spared. (C) 2000 Elsevier Science B.V. All r ights reserved.