Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI2in rats
| Autor: | Sumito Mizuguchi, Katsuharu Arai, Takeo Saeki, Kazuhisa Kamata, Katsunori Saigenji, Masataka Majima, Makoto Katori, Takashi Ohno |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Physiology Calcitonin Gene-Related Peptide Indomethacin Neuropeptide Hemodynamics Endogeny Sodium Chloride Pharmacology Calcitonin gene-related peptide Microcirculation Rats Sprague-Dawley chemistry.chemical_compound Venules Physiology (medical) medicine Animals Ethanol Hepatology Stomach Anti-Inflammatory Agents Non-Steroidal Gastroenterology Central Nervous System Depressants Adaptation Physiological Epoprostenol Peptide Fragments Rats Surgery Sprague dawley medicine.anatomical_structure chemistry Gastric Mucosa Regional Blood Flow Irritants |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 286:G68-G75 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00538.2002 |
| Popis: | 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 PGE2or beraprost sodium (a PGI2analog) 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 PGE2was 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 PGI2but not by PGE2. |
| Databáze: | OpenAIRE |
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