Possible involvement of endothelium-granulocyte interaction in acute gastric mucosal lesions—Participation of platelet-activating factor—

Abstract

Gastric microcirculatory disturbances induced by intermittent electrical stimuli (irritation) on the gastric artery produced acute gastric mucosal lesions in the rat stomach. In this experimental model, participation of platelet-activating factor (PAF) in granulocyte-endothelium interaction were evaluated.
Laser doppler flowmetry revealed that post-ischemic hyperemia was observed just after the irritation and the flow was significantly decreased after this hyperemic state. Mucosal tissue-type plasminogen activator (t-PA) activity was also elevated just after the irritation and still more increased thirty minutes after the stimuli. Moreover, both luminol-dependent chemiluminescence activity of regional blood sample and myeloperoxidase activity in gastric mucosa were remarkably increased thirty minutes after the irritation. A newly developed PAF-antagonist, CV-6209 attenuated the local fibrinolytic activity, granulocyte-mediated oxidative stress and the alteration of mucosal blood flow, and significantly diminished the gastric ulcer formation.
The present study suggests that PAF may cause the excessive fibrinolytic activity and granulocyte-mediated oxidative stress on mucosal microvasculature during acute gastric ulcer formation.