Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats.
BACKGROUND
We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation.


METHODS
A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry.


RESULTS
In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086.


CONCLUSIONS
The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.
Atuma
C
C
Dept. of Physiology, Uppsala University, Sweden.
Engstrand
L
L
Holm
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure; D005753:Gastric Mucosa / Q000098:blood supply*; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008407:Mast Cells; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007665:Ketotifen