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MUCOSAL BIOLOGY

Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI₂ in rats

Departments of ¹Internal Medicine and ²Pharmacology, Kitasato University School of Medicine, and ³Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Kanagawa 228-8555, Japan

Submitted 20 December 2002 ; accepted in final form 9 August 2003

Pretreatment with a mild irritant such as 1 M NaCl prevented ethanol-induced mucosal injury, which was abolished by indomethacin, suggesting involvement of endogenous PGs. With the use of intravital microscopy, we investigated the mechanism in microcirculation whereby a mild irritant prevents ethanol-induced mucosal injury. Microcirculation of the basal part of gastric mucosa in anesthetized rats was observed through a window with transillumination. Diameters of arterioles, collecting venules, and venules were measured with an electric microscaler. One molar NaCl alone caused dilation of arterioles and constrictions of collecting venules and venules, which were inhibited by indomethacin. Ethanol (50%) applied to mucosa constricted collecting venules and venules but dilated arterioles. Constriction of collecting venules resulted in mucosal congestion. Pretreatment with 1 M NaCl inhibited ethanol-induced constrictions of collecting venules and venules, and administration of indomethacin or a calcitonin gene-related peptide (CGRP) antagonist, CGRP-(8–37), abolished elimination of constrictions. Topical application (1 nM–10 µM) of PGE₂ or beraprost sodium (a PGI₂ analog) to microvasculature markedly and dose-dependently dilated arterioles, whereas that of PGE₂, but not beraprost, slightly constricted collecting venules. Pretreatment of microvasculature with a nonvasoactive concentration of PGE₂ (100 nM) or beraprost (1 nM) completely inhibited ethanol-induced constriction of collecting venules. The inhibitory effect of beraprost but not of PGE₂ was abolished by CGRP-(8–37). Present results suggest that the mechanism whereby 1 M NaCl prevents ethanol-induced injury is elimination of constrictions of collecting venules and venules by CGRP whose release may be enhanced by PGI₂ but not by PGE₂.

microcirculation; gastric mucosal blood flow; ethanol; prostaglandin I₂

This article has been cited by other articles:

				Y. Hattori, T. Ohno, T. Ae, T. Saeki, K. Arai, S. Mizuguchi, K. Saigenji, and M. Majima Gastric mucosal protection against ethanol by EP2 and EP4 signaling through the inhibition of leukotriene C4 production Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G80 - G87. [Abstract] [Full Text] [PDF]