Document Detail


Beneficial effects of angiotensin I converting enzyme inhibitor on post-ischemic contractile function of perfused rat heart.
MedLine Citation:
PMID:  8877776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study was undertaken to determine whether trandolaprilat, an active form of angiotensin I converting enzyme (ACE) inhibitor, may improve ischemia/reperfusion-induced contractile dysfunction and metabolic derangement of isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted in a small recovery of post-ischemic left ventricular developed pressure (LVDP), a sustained increase in left ventricular end-diastolic pressure, an increase in the release of creatine kinase and ATP metabolites from the perfused heart, and changes in myocardial sodium, potassium, calcium and magnesium contents. Treatment with 10-100 microM of trandolaprilat for the last 10 min of pre-ischemia recovered approximately 50-90% of pre-ischemic LVDP during reperfusion, whereas that with 30-100 microM of enalaprilat restored approximately 55-65% of the pre-ischemic LVDP. Treatment with either trandolaprilat or enalaprilat at these concentrations attenuated the release of creatine kinase and ATP metabolites into the perfusate during reperfusion. Treatment with 30 microM trandolaprilat suppressed ischemia/reperfusion-induced changes in myocardial ion content. Treatment with bradykinin during the last 10 min of pre-ischemia also resulted in a post-ischemic contractile recovery with a degree similar to that of the trandolaprilat-treated hearts. E4177, an AT1-antagonist, showed no effect on ischemia/reperfusion-induced changes in cardiac parameters. The enhancement of post-ischemic contractile recovery by the ACE inhibitor was abolished by treatment with either Hoechst 140, a bradykinin (BK2) antagonist, or diclofenac, a cyclooxygenase inhibitor. These results suggest that trandolaprilat is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts and altered BK metabolism is, at least in part, involved in this effect.
Authors:
K Tanonaka; T Kamiyama; A Takezono; K Sakai; S Takeo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  28     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-01-29     Completed Date:  1997-01-29     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1659-70     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Analysis of Variance
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Animals
Bradykinin / pharmacology
Cations / metabolism
Creatine Kinase / metabolism
Enalaprilat / pharmacology
Indoles / therapeutic use*
Male
Myocardial Contraction / drug effects*
Myocardial Reperfusion Injury / drug therapy*
Rats
Rats, Wistar
Receptors, Angiotensin / antagonists & inhibitors
Receptors, Bradykinin / antagonists & inhibitors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Cations; 0/Indoles; 0/Receptors, Angiotensin; 0/Receptors, Bradykinin; 56-65-5/Adenosine Triphosphate; 58-82-2/Bradykinin; 83601-86-9/trandolaprilat; 84680-54-6/Enalaprilat; EC 2.7.3.2/Creatine Kinase

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


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