Document Detail


Tissue endothelin-1 levels in perfused rat heart following stimulation with agonists and in ischaemia and reperfusion.
MedLine Citation:
PMID:  8523455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to compare coronary and interstitial endothelin-1 (ET-1) levels in perfused rat hearts under several experimental conditions, because the cardiac tissue concentration of ET-1 is not clear. Hearts were perfused in an upside-down position with a colloid-free buffer at a constant flow rate of 9 ml/min/g heart wet weight, and immunoreactive ET-1 was determined in timed collections of coronary effluent and interstitial transudate produced by the ventricles and appearing on their surface. Basal ET-1 release into effluent was 0.26 +/- 0.007 pg/min/g, and 0.005 +/- 0.0012 pg/min/g in transudate. Basal ET-1 concentration was 0.11 +/- 0.005 pg/ml (transudate) and 0.03 +/- 0.002 pg/ml (effluent), indicating four-fold higher transudate than effluent levels (P < 0.05). Following perfusion of hearts with collagenase to remove endothelial cells, ET-1 release into effluent was reduced to one-third and completely abolished in transudate, indicating that the peptide originated from the vascular endothelium. Perfusion of hearts with angiotensin II (0.1 mumol/l) or thrombin (5 U/ml) increased coronary perfusion pressure and ET-1 secretion, but little affected the transudate/effluent ET-1 concentration ratio (5.5 and 3.2, respectively). When coronary flow was reduced to ischaemic level (1 ml/min/g over several hours), ET-1 secretion rates into effluent were decreased by 55-65%, but increased three- to four-fold on reperfusion at normal flow (P < 0.05). The ET-1 concentrations in both fluids were still always below 1 pg/ml. No change in coronary perfusion pressure compared to time-matched normoxic controls was observed. In the presence of the ET-1 converting enzyme inhibitor, phosphoramidon (1.7 mumol/l), ischaemia-induced increases of ET-1 secretion were attenuated, and this was accompanied by a time-dependent rise in coronary perfusion pressure up to 60% (P < 0.05). These are the first measurements of endogenous cardiac tissue ET-1 levels; they do not support a vasoconstrictor (pro-ischaemic) action of endogenous ET-1 in rat hearts following ischaemia/reperfusion, but rather point to a possible vasodilator role of the peptide under these conditions.
Authors:
F Brunner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  27     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1996-01-25     Completed Date:  1996-01-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1953-63     Citation Subset:  IM    
Affiliation:
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / pharmacology*
Animals
Coronary Vessels / metabolism*
Endothelins / agonists,  metabolism*
Endothelium / metabolism,  physiopathology
Myocardial Ischemia / metabolism*,  physiopathology
Myocardial Reperfusion Injury / metabolism*,  physiopathology
Myocardium / metabolism*
Perfusion
Rats
Rats, Sprague-Dawley
Thrombin / pharmacology*
Vasoconstrictor Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Endothelins; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; EC 3.4.21.5/Thrombin

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