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, indomethacin (10 mg kg(-1), s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled L-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions 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, whereas both the ileum and colon are spared.
Evans
S M
SM
Glaxo-Wellcome Research and Development, Hertfordshire, UK.
László
F
F
Whittle
B J
BJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D004751:Enteritis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D004790:Enzyme Induction; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000473:pathology; D007420:Intestine, Large / Q000201:enzymology / Q000473:pathology*; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009928:Organ Specificity; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D007213:Indomethacin