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Mechanisms of Helicobacter pylori-Induced Rat Gastric Mucosal Microcirculatory Disturbances In Vivo

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Abstract

The exact mechanisms by which Helicobacter pylori infection results in gastric mucosal injury are unclear. However, it has been demonstrated that surface protein extracts of the bacterium can induce a number of disturbances within the rat gastric mucosal microcirculation, including platelet aggregation and macromolecular leakage (MML) of labeled albumin. This study aimed to determine the mechanisms involved in inducing these events using the technique of fluorescent in vivo microscopy. Male Wistar rats were pretreated with either ketotifen, a mast cell stabilizer (1 mg/kg), pyrilamine, an H1-receptor antagonist (30 mg/kg), hexanolamine-PAF, a PAF-receptor antagonist (10 μg/kg), l-arginine, the nitric oxide precursor (300 mg/kg) or vehicle, saline. Then 0.5 ml of H. pylori extract was administered to the exteriorized gastric mucosa of the anesthetized rat. Alterations in fluorescein-labeled albumin leak, vessel diameters, and acridine red-labeled leukocyte and platelet activity were determined over a 2-hr period. Saline pretreated animals demonstrated significant MML with a peak at 5 min (11%, P < 0.02). This 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 of platelet emboli and thrombi were observed within mucosal capillaries and postcapillary venules with vehicle pretreatment; this was prevented with hexanolamine-PAF and l-arginine, but not with ketotifen and pyrilamine. In conclusion, these studies demonstrate that more than one mediator is involved in inducing the rat gastric mucosal microcirculatory disturbances associated with H. pylori administration. Mast cells and histamine are linked to MML, with PAF, probably not derived from mast cells, involved in platelet activation.

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Authors and Affiliations

  1. Department of Surgical and Anaesthetic Sciences, Royal Hallamshire Hospital, Sheffield, UK

    N. Kalia, K.D. Bardhan, M.W.R. Reed, S. Jacob & N.J. Brown

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  1. N. Kalia
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  2. K.D. Bardhan
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  3. M.W.R. Reed
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  4. S. Jacob
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  5. N.J. Brown
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Kalia, N., Bardhan, K., Reed, M. et al. Mechanisms of Helicobacter pylori-Induced Rat Gastric Mucosal Microcirculatory Disturbances In Vivo. Dig Dis Sci 45, 763–772 (2000). https://doi.org/10.1023/A:1005456029396

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