Premium
The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat
Author(s) -
BoughtonSmith Nigel K.,
Evans Steven M.,
Laszlo Ferenc,
Whittle Brendan J.R.,
Moncada Salvador
Publication year - 1993
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.1476-5381.1993.tb13940.x
Subject(s) - jejunum , nitric oxide synthase , medicine , endocrinology , lipopolysaccharide , nitric oxide , arginine , citrulline , vascular permeability , chemistry , pharmacology , biology , biochemistry , amino acid
1 The effect of endotoxin ( E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat. 2 Under resting conditions, a calcium‐dependent constitutive NOS, determined by the conversion of radiolabeled l ‐arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue. 3 Administration of endotoxin (3 mg kg −1 , i.v.) led, after a 2 h lag period, to the appearance of calcium‐independent NOS activity in the colon and jejunum ex vivo , characteristic of the inducible NOS enzyme. 4 Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin. 5 Pretreatment with dexamethasone (1 mg kg −1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin. 6 Administration of the NO synthase inhibitor N G ‐monomethyl‐ l ‐arginine (12.5–50 mg kg −1 , s.c.) 3 h after endotoxin injection, dose‐dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by l ‐arginine (300 mg kg −1 , s.c). 7 These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.