Mechanisms of Helicobacter pylori-induced rat gastric mucosal microcirculatory disturbances in vivo

The exact mechanisms by which Helicobacter pylori infection results in gast ric mucosal injury are unclear. However, it has been demonstrated that surf ace protein extracts of the bacterium can induce a number of disturbances w ithin the rat gastric mucosal microcirculation, including platelet aggregat ion and macromolecular leakage (MML) of labeled albumin. This study aimed t o determine the mechanisms involved in inducing these events using the tech nique of fluorescent in vivo microscopy. Male Wistar rats were pretreated w ith either ketotifen, a mast cell stabilizer (1 mg/kg), pyrilamine, an H-1- receptor antagonist (30 mg/kg), hexanolamine-PAF, a PAF-receptor antagonist (10 mu g/kg), L-arginine, the nitric oxide precursor (300 mg/kg) or vehicl e, saline. Then 0.5 mi of H. pylori extract was administered to the exterio rized gastric mucosa of the anesthetized rat. Alterations in fluorescein-la beled albumin leak, vessel diameters, and acridine red-labeled leukocyte an d platelet activity were determined over a 2-hr period. Saline pretreated a nimals demonstrated significant MML with a peak at 5 min (11%, P < 0.02). T his was prevented with ketotifen and pyrilamine, but not with hexanolamine- PAF (17.5%, P < 0.05) and L-arginine (13%, P < 0.05). Significant numbers o f platelet emboli and thrombi were observed within mucosal capillaries and postcapillary venules with vehicle pretreatment; this was prevented with he xanolamine-PAF and L-arginine, but not with ketotifen and pyrilamine. In co nclusion, these studies demonstrate that more than one mediator is involved in inducing the rat gastric mucosal microcirculatory disturbances associat ed with H. pylori administration. Mast cells and histamine are linked to MM L, with PAF, probably not derived from mast cells, involved in platelet act ivation.