Document Detail


Regional distribution of endothelin-1 and endothelin converting enzyme-1 in porcine endotoxemia.
MedLine Citation:
PMID:  11580117     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelin-1 (ET-1) levels are markedly increased in sepsis. Since ET-1 is primarily transcriptionally regulated, there should be a corresponding increase in pre-pro-endothelin-1 (ppET-1). Our objective was to determine whether ppET-1 is increased in pigs with a low systemic vascular resistance. We also examined the distribution of ET-1 and the regulation of endothelin-converting enzyme 1 (ECE-1), the rate limiting enzyme in ET-1 production. We anesthetized and ventilated 16 pigs. We measured arterial, pulmonary, and central venous pressures, as well as cardiac output. ET-1 was measured by radioimmunoassay in plasma and in multiple tissues. We infused 20 microg/kg of endotoxin over 2 h and then sacrificed the animals. ppET-1 and ECE-1 mRNA were assessed by Northern analysis. We performed immunohistochemistry for the assessment of tissue ET-1 and ECE-1. The systemic vascular resistance rose at 30 min, but fell by 120 min. Plasma ET-1 more than doubled by 2 h. However, there was no change in the concentration of ET-1 in any tissue except in the pulmonary artery. By immunohistochemistry, there was also no change in ET-1 in aorta, vena cava, heart, lung, liver, and kidney. Distribution of ECE-1 followed that of ET-1 on immunohistochemistry. There was a significant increase in ppET-1 mRNA in liver, kidney papillae, and vena cava, and a tendency for an increase in other tissues. This was paralleled by an increase in ECE-1 mRNA. In conclusion, the amount of ECE-1 mRNA and protein parallel those of ET-1. Endotoxemia is associated with a marked increase in plasma ET-1 and an increase in ppET-1 and ECE-1 mRNA in multiple tissues; however, there was no significant change in tissue ET-1 except in the pulmonary artery. The rise in plasma levels without a change in tissue levels suggests a greater release into the vasculature in sepsis than under normal conditions.
Authors:
S Magder; D Javeshghani; P Cernacek; A Giaid
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  16     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-02     Completed Date:  2002-03-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  320-5     Citation Subset:  IM    
Affiliation:
Department of Medicine and Physiology, McGill University, Montréal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid Endopeptidases / genetics,  metabolism*
Blotting, Northern
Endothelin-1 / genetics,  metabolism*
Endotoxemia / metabolism*,  physiopathology
Hemodynamics
Immunohistochemistry
Metalloendopeptidases
Swine
Chemical
Reg. No./Substance:
0/Endothelin-1; EC 3.4.23.-/Aspartic Acid Endopeptidases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.71/endothelin-converting enzyme

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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