Lipoxygenase metabolites in the rat gastric microvascular response to intragastric ethanol

The role of lipoxygenase metabolites in ethanol-induced gastric mucosal injury and submucosal microvascular change in the rat was studied by in vivo microscopy. Intragastric ethanol-instillation caused marked submucosal venular constriction, dilatation of small arterioles, and corpus mucosal gross lesion formation. The venoconstriction was greater in the lesion than in the nonlesion area. Intragastric pretreatment with either BW755C, a lipoxygenase inhibitor, or Rioprostil, a synthetic prostaglandin E1 analogue, significantly inhibited both the ethanol-induced venoconstriction and the gross lesion formation. In contrast, pretreatment by the submucosal application of either BW755C (50 micrograms/ml) or Rioprostil (50-500 ng/ml) had no effect on either the submucosal venoconstriction or the mucosal lesion formation. In conclusion, leukotrienes released from the gastric mucosa appear to be involved in the ethanol-induced submucosal venoconstriction associated with gastric mucosal injury. Prostaglandin pretreatment protects against this venoconstriction and gross lesion by a mucosal effect but not by a direct effect on submucosal venules.