Linked Life Data

11072871

Source:http://linkedlifedata.com/resource/pubmed/id/11072871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2000-11-9
pubmed:abstractText
The enhanced production of endothelial cell-derived vasoactive mediators and the activation of mast cells (MCs) have been implicated in the pathogenesis of mucosal damage during ischemia and reperfusion injuries. The first objective of our study was to define the in vivo relation between endothelin-1 (ET-1) and the MC system. Secondly, we determined whether pretreatment with ET receptor antagonists would attenuate MC responses to exogenous ET-1. In the first series of experiments, increasing doses of ET-1 (0. 1, 1 and 3 nmol/kg i.v.) were administered to anesthetized rats. In the second series, the animals were pretreated with equimolar doses of the ET-A receptor antagonist BQ-610 or ETR-P1/fl peptide, and the ET-B receptor antagonist IRL-1038. Intestinal perfusion changes and macrohemodynamics were recorded, and the proportion of degranulated MCs was determined in ileal biopsies. The average mucosal thickness was recorded with an image analysis system. ET-1 induced dose-dependent alterations in the hemodynamic and morphological parameters and caused pronounced mucosal injury, with a significant reduction in villus height. The ratio of degranulated MCs was similar in all ET-treated groups (77%, 82% and 86%) to that observed in animals subjected to 15-min ischemia and 60-min reperfusion (85% degranulation). Pretreatment with BQ-610 and ETR-P1/fl peptide attenuated the ET-1 induced alterations in the hemodynamic parameters and decreased structural injury to the mucosa. ET-induced MC degranulation was significantly inhibited by the ET-A receptor antagonists, but not by IRL-1038. These results indicate that elevated levels of circulating ET-1 might induce intestinal mucosal tissue injury and MC degranulation via activation of ET-A receptors, and raise the possibility that ET-A receptor antagonist administration could exert a potentially beneficial effect through a mechanism other than the blockade of vasoconstriction in pathologies associated with an increased ET-1 release.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1947-58
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11072871-Amino Acid Sequence, pubmed-meshheading:11072871-Animals, pubmed-meshheading:11072871-Blood Pressure, pubmed-meshheading:11072871-Cell Degranulation, pubmed-meshheading:11072871-Dose-Response Relationship, Drug, pubmed-meshheading:11072871-Endothelin-1, pubmed-meshheading:11072871-Endothelins, pubmed-meshheading:11072871-Erythrocyte Count, pubmed-meshheading:11072871-Intestinal Mucosa, pubmed-meshheading:11072871-Intestine, Small, pubmed-meshheading:11072871-Ischemia, pubmed-meshheading:11072871-Male, pubmed-meshheading:11072871-Mast Cells, pubmed-meshheading:11072871-Molecular Sequence Data, pubmed-meshheading:11072871-Oligopeptides, pubmed-meshheading:11072871-Peptide Fragments, pubmed-meshheading:11072871-Peptides, pubmed-meshheading:11072871-Rats, pubmed-meshheading:11072871-Rats, Sprague-Dawley, pubmed-meshheading:11072871-Receptor, Endothelin A, pubmed-meshheading:11072871-Receptor, Endothelin B, pubmed-meshheading:11072871-Receptors, Endothelin, pubmed-meshheading:11072871-Reperfusion
pubmed:year
2000
pubmed:articleTitle
Endothelin-1 induces mucosal mast cell degranulation in the rat small intestine.
pubmed:affiliation
Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary. szalay@expsur.szote.u-szeged.hu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't