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Early phase microvascular interactions in rat jejunum between nitric oxide and vasopressin following indomethacin administration
Author(s) -
LÁSZLÓ FERENC,
WHITTLE BRENDAN
Publication year - 1998
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.1998.01745.x
Subject(s) - vasopressin , nitric oxide synthase , medicine , jejunum , nitric oxide , endogeny , vascular permeability , endocrinology , arginine , antagonist , pharmacology , evans blue , chemistry , receptor , biochemistry , amino acid
The involvement of endogenous vasopressin in the actions 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 after 1 h, as determined by the leakage of radiolabelled serum albumin. In contrast, when indomethacin (10 mg/kg, s.c.) was injected concurrently with L ‐NAME (2–10 mg/kg, s.c.), significant dose‐dependent plasma leakage occurred in the jejunum. Pretreatment with L ‐arginine (300 mg/kg s.c.) 15 min prior to L ‐NAME prevented these changes in microvascular permeability. Moreover, pretreatment with the vasopressin pressor‐receptor antagonist, d(CH 2 ) 5 Tyr(Me)AVP (0.01– 0.2 μg/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 vasopressin in the rat jejunum. This suggests a protective role of NO, formed by constitutive NO synthase, counteracting effectively the deleterious actions of endogenous vasopressin.