Document Detail

Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion.
MedLine Citation:
PMID:  8590976     Owner:  NLM     Status:  MEDLINE    
1. This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (KATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55 +/- 4% (n = 11). ET-1 (0.3 nmol kg-1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 +/- 2%, n = 4). A lower dose of ET-1 (0.03 nmol kg-1) resulted in a significant reduction in infarct size (infarct size 43 +/- 3%; P < 0.05, n = 16). The higher dose (0.3 nmol kg-1), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3. The reduction in infarct size afforded by ET-1 (0.03 nmol kg-1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg-1) and 5-HD (5 mg kg-1), (infarct size 59 +/- 3 and 63 +/- 4% respectively; n = 4-9). 4. We propose that ET-1 reduces infarct size by opening KATP channels.
E J Hide; J Piper; C Thiemermann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  116     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1996-04-04     Completed Date:  1996-04-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2597-602     Citation Subset:  IM    
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
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MeSH Terms
Adenosine Triphosphate / physiology*
Anti-Arrhythmia Agents / pharmacology
Arterial Occlusive Diseases / complications
Blood Pressure / drug effects
Coronary Disease / complications
Decanoic Acids / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelins / therapeutic use*
Glyburide / pharmacology
Heart Rate / drug effects
Hydroxy Acids / pharmacology
Myocardial Infarction / etiology,  prevention & control*
Myocardial Ischemia / complications*,  etiology
Myocardial Reperfusion Injury / prevention & control*
Potassium Channels / drug effects*,  physiology
Sensitivity and Specificity
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Decanoic Acids; 0/Endothelins; 0/Hydroxy Acids; 0/Potassium Channels; 10238-21-8/Glyburide; 56-65-5/Adenosine Triphosphate; 624-00-0/5-hydroxydecanoic acid

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