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Role of nitric oxide in maintaining vascular integrity in endotoxin‐induced acute intestinal damage in the rat
Author(s) -
Hutcheson Iain R.,
Whittle Brendan J.R.,
BoughtonSmith Nigel K.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14163.x
Subject(s) - omega n methylarginine , lipopolysaccharide , nitric oxide , phenylephrine , arginine , pharmacology , chemistry , intestinal mucosa , vascular permeability , endogeny , medicine , blood pressure , endocrinology , nitric oxide synthase , biochemistry , amino acid
1 The role of endogenous nitric oxide (NO) in maintaining intestinal vascular integrity following acute endotoxin ( E. coli . lipopolysaccharide) challenge was investigated in the anaesthetized rat by use of N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA), a selective inhibitor of NO synthesis. 2 l ‐NMMA (10–50 mg kg −1 , i.v.) pretreatment enhanced both the macroscopic and histological intestinal damage and the increases in vascular permeability, measured as the leakage of [ 125 I]‐labelled human serum albumen, induced after 15 min by endotoxin (50 mg kg −1 , i.v.). 3 The effects of l ‐NMMA (50 mg kg −1 , i.v.) were enantiomer specific, as d ‐NMMA had no effect. Furthermore, these effects were reversed by l ‐arginine (300 mg kg −1 , i.v.), the precursor of NO synthesis but not by d ‐arginine (300 mg kg −1 , i.v.). 4 l ‐NMMA (10–50 mg kg −1 , i.v.) increased mean systemic arterial blood pressure but this does not appear to be the mechanism by which endotoxin‐induced intestinal damage was enhanced, since similar systemic pressor responses induced by phenylephrine (10 μg kg −1 min −1 , i.v.), had no such effect. 5 The results suggest that synthesis of NO from l ‐arginine has a role in maintaining the microvascular integrity of the intestinal mucosa following acute endotoxin challenge.