The effect of indomethacin following the concurrent administration of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on acute intestinal microvascular permeability has been investigated in the rat. Administration of indomethacin (10 mg/kg, s.c.) or L-NAME (10 mg/kg, s.c.) alone did not affect jejunal and ileal vascular permeability over a 12 h period, as determined by the leakage of radiolabelled serum albumin. By contrast, when indomethacin (10 mg/kg, s.c.) was injected concurrently with L-NAME (2-10 mg/kg, s.c.) significant time-dependent plasma leakage occurred in intestinal tissues over 12 h, being apparent within 1 h. Pretreatment with L-arginine (300 mg/kg, s.c.) 15 min prior L-NAME prevented these changes in microvascular permeability. Likewise, pretreatment with the platelet-activating factor receptor antagonist, WEB 2086 ((3-[4-(2- chlorophenyl)-9-methyl-6H-thienol[3,2-f][1,2,4]triazolo-[4,3- a][1,4]diazepine-2-yl]-1-(4-morpholynil)-1-propanone), 0,1-1 mg/kg, s.c.) dose-dependently attenuated such damage. These findings suggest that following indomethacin administration, the early inhibition of NO synthase leads to acute microvascular injury involving platelet-activating factor in the rat jejunum and ileum, indicating a protective role of NO, formed by constitutive NO synthase.
- Inflammation, intestinal
- N(G)-Nitro-L-arginine methyl ester (L- NAME)
- Nitric oxide (NO)
- PAF (platelet-activating factor)
- Plasma leakage
- WEB 2086
ASJC Scopus subject areas