Organ specific early endothelin release in cysteamine-induced duodenal ulcération in rats

A. Vincze, Z. S. Sandor, A. Pedram, E. R. Levin, S. Szabo

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Abstract

Previous studies showed that endothelins (ET) play a role in the pathogenesis and diagnosis of acute gastric hemorrhagic erosions. The earliest duodenal lesions induced by cysteamine (HS-CH2-CH-NH2) ultrastructurally and light microscopically resemble ischémie damage. The duodenal ulcerogen in 15-30 min increased vascular permeability in the duodenal mucosa. We now tested the hypothesis that local release of endothelin-1 (ET-1) might be one of mediators of early vascular and tissue injury in duodenal ulcération. Groups of Sprague-Dawley female rats were given a single dose of the cysteamine HC1 (25 mg/100 g) by gavage, and were killed 15, 30 and 60 min later. The duodenal mucosal ET-1 (pg/mg protein), measured by RIA, were 88.0 ±18.3, 1015.4 ±350.3 (p 0.01), 462.6 + 158.2 (p 0.01) and 202.5 ±30.6 (p 0.05) at 0, 15, 30 and 60 min after cysteamine, respectively, while the gastric mucosal and the serum levels did not change. This early ET-1 release was not found in rats treated with equimolar doses of ethanolamine (HO-CH2-CH2-NH2), which exerts no duodenal ulcerogenic activity. To relate the elevated levels of ET in the duodenal mucosa to duodenal ulcération, groups of rats were pretreated with anti-ET-1 serum (1:100 dilution, 0.2 ml/lOO g, iv, xl or x3) 30 min before the first or all 3 doses of cysteamine HC1. The animals were killed on the 3rd day when the duodenal ulcer sizes were 13.0 ±5.1 mm2 in the controls, and 5.9 ± 0.8 (p = 0.23) and 3.0 ± 1.4 mm2 (p = 0.05) after 1 or 3 doses of anti-ET-1, respectively. Thus, endogenous ET may play a role in the development of acute duodenal ulcers, and control of ET release might represent a novel pharmacologie tool for ulcer prevention.

Original languageEnglish
Number of pages1
JournalProceedings of the Western Pharmacology Society
Volume39
Publication statusPublished - Dec 1 1996

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ASJC Scopus subject areas

  • Pharmacology

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