Document Detail

Inhibition of granulocyte-derived proteases reduces the increase in plasma endothelin associated with myocardial ischemia in the pig.
MedLine Citation:
PMID:  8874778     Owner:  NLM     Status:  MEDLINE    
Plasma endothelin (ET) is increased in association with myocardial infarction. The aim of the present study was to get insight into the mechanisms behind this ischemia-induced increase in plasma ET. Since granulocytes increase ET production in vitro, we examined to what extent inhibition of granulocyte-derived proteases could reduce the increase in plasma ET observed in association with myocardial ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min left anterior descending coronary artery occlusion followed by 210 min reperfusion (n = 7). Arterial plasma ET increased in an untreated control group (n = 7) from 5.0 +/- 0.6 (mean +/- SEM) fmol . ml-1 before myocardial ischemia to 6.1 +/- 0.6 fmol . ml. at 90 min ischemia and reached a maximum of 6.8 +/- 0.9 fmol . ml-1 at 90 min reperfusion. The increase in plasma ET associated with myocardial ischemia was almost completely abolished in the Eglin C treated group (p = 0.005). Plasma ET in the Eglin C treated animals was 4.7 +/- 0.4, 4.7 +/- 0.4, and 4.6 +/- 0.4 fmol . ml-1 before myocardial ischemia, at 90 min ischemia, and at 90 min reperfusion, respectively. Our study suggests a role for granulocyte-derived proteases in the increase in plasma ET associated with myocardial ischemia. We have shown that the increase in plasma ET associated with myocardial ischemia was reduced by inhibition of granulocyte-derived proteases using the selective protease inhibitor Eglin C.
T Tønnessen; A Ilebekk; P A Naess; G Christensen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic research in cardiology     Volume:  91     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:    1996 Jul-Aug
Date Detail:
Created Date:  1997-01-14     Completed Date:  1997-01-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  289-95     Citation Subset:  IM    
Institute for Experimental Medical Research Ullevål Hospital, Oslo, Norway.
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MeSH Terms
Cathepsin G
Cathepsins / antagonists & inhibitors,  drug effects
Chymotrypsin / antagonists & inhibitors,  drug effects
Endothelins / blood*
Enzyme Inhibitors / pharmacology
Granulocytes / drug effects*,  enzymology
Hemodynamics / drug effects
Myocardial Ischemia / physiopathology*
Pancreatic Elastase / antagonists & inhibitors,  drug effects
Serine Endopeptidases
Serpins / pharmacology*
Reg. No./Substance:
0/Endothelins; 0/Enzyme Inhibitors; 0/Proteins; 0/Serpins; 0/eglin proteinase inhibitors; EC 3.4.-/Cathepsins; EC 3.4.21.-/Serine Endopeptidases; EC; EC G; EC Elastase

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