LIPOPOLYSACCHARIDE OF HELICOBACTER-PYLORI PROTECTS GASTRIC-MUCOSA VIAGENERATION OF NITRIC-OXIDE

Citation
T. Brzozowski et al., LIPOPOLYSACCHARIDE OF HELICOBACTER-PYLORI PROTECTS GASTRIC-MUCOSA VIAGENERATION OF NITRIC-OXIDE, Journal of Physiology and Pharmacology, 48(4), 1997, pp. 699-717
Citations number
41
Language
INGLESE
art.tipo
Article
ISSN journal
0867-5910
Volume
48
Issue
4
Year of publication
1997
Pages
699 - 717
Database
ISI
SICI code
0867-5910(1997)48:4<699:LOHPGV>2.0.ZU;2-D
Abstract
Lipopolysaccharide (LPS) has been proposed to act as the major virulen ce factor in Helicobacter pylori (Hp)-infected stomach but its action on mucosal integrity has been little studied. We determined the effect s of LPS of Hp, expressing cytotoxic antigens CagA and VacA on acute g astric lesions induced by 100% ethanol, mucosal blood flow (GBF) and e xpression of constitutive nitric oxide (NO) synthase (cNOS) mRNA and i nducible NO synthase (iNOS) mRNA in gastric mucosa using RT-PCR. Two m ajor series (A and B) of rats were employed; A - with suppressed NOS a ctivity by nonspecific NOS inhibitor, such as N-G-nitro-L-arginine met hyl ester, (L-NAME) (5 mg/kg i.v.), or by specific iNOS inhibitor, N-G -(1-lmmunoethyl) lysine (L-NIL) (30 mg/kg i.g.), or with inhibited ind uction of NOS activity by dexamethasone (2 mg/kg i.p.) and series B - vehicle (saline)-treated controls. LPS (0.01-1.0 mg/kg) given i.p. att enuated dose-dependently ethanol-induced mucosal lesions and this prot ective effect was accompanied by a rise in the GBF and excessive mucos al production and luminal release of NC). LPS (I mg/kg i.p.) administe red at lower dose (1 mg/kg i.p.) to rats without ethanol instillation significantly elevated GBF and luminal release of NO, while higher dos es of LPS (20 and 40 mg/kg i.p.) or SNAP (6 mg/kg), which produced sys temic hypotension, were not protective. Suppression of NOS activity by I,retreatment with standard dose of L-NAME or L-NIL and inhibition of NOS induction by treatment with dexamethasone reversed the protective and hyperemic effects of LPS and this reversal was significantly anta gonized by the addition of the substrate fbr cNOS, L-arginine, but not D-arginine. Administration of L-NAME, L-NIL or dexamethasone, complet ely abolished the enhanced mucosal NO production and the hyperemia ind uced by LPS in rats without or with topical application of ethanol. Ex pression of cNOS was detected by RT-PCR in the intact mucosa but inten se signals for expression of both cNOS and iNOS were detected by RT-PC R in the gastric mucosa of LPS-treated rats. We conclude that parenter al LPS protects gastric mucosa from acute ethanol-induced damage via a n increase in mucosal microcirculation mediated by NO due to the overe xpression of iNOS and activation of arginine-NO-system.