| Bradykinin-dependent cardioprotective effects of losartan against ischemia and reperfusion in rat hearts. | |
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MedLine Citation:
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PMID: 10226867 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is unclear whether losartan, an angiotensin II type 1 (AT1) receptor antagonist, protects the heart against acute ischemia-reperfusion injury. Therefore we evaluated cardiac protection conferred by pre- and postischemic treatment as well as by exclusive postischemic treatment with losartan. Furthermore, we sought to determine both the extent of this protection and its dependence on bradykinin in comparison with quinaprilat, a cardioprotective angiotensin-converting enzyme inhibitor. Cardiac protection was assessed as recovery of coronary flow, left ventricular developed pressure, phosphocreatine, and adenosine triphosphate (ATP) in isolated perfused rat hearts after 15 min of global ischemia and 30 min of postischemic reperfusion. We found that, in hearts pre- and postischemically treated with losartan (1 microM) or quinaprilat (0.1 microM), these variables all recovered significantly better than those in untreated control hearts. In hearts that were only postischemically treated with losartan, these variables also recovered significantly better than those in control hearts. In contrast, in hearts treated with the combination of the bradykinin B2 receptor antagonist Hoe 140 with quinaprilat or losartan, the recovery of the variables no longer differed from that in control hearts. In conclusion, losartan protects the heart against acute ischemia-reperfusion injury. This protection can be achieved by pre- and postischemic treatment as well as by exclusive postischemic treatment with losartan. Furthermore, the extent of this protection is equivalent to that conferred by quinaprilat and, unexpectedly, dependent on bradykinin. |
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Authors:
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P Zhu; C E Zaugg; P S Hornstein; P R Allegrini; P T Buser |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 33 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1999 May |
Date Detail:
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Created Date: 1999-06-11 Completed Date: 1999-06-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 785-90 Citation Subset: IM |
Affiliation:
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Cardiovascular Research Group, University Hospital Basel, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Angiotensin II / metabolism* Angiotensin-Converting Enzyme Inhibitors / pharmacology Animals Bradykinin / physiology* Coronary Circulation / drug effects Isoquinolines / pharmacology Losartan / pharmacology* Male Myocardial Reperfusion Injury / metabolism, physiopathology, prevention & control* Myocardium / metabolism Phosphocreatine / metabolism Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin / antagonists & inhibitors* Tetrahydroisoquinolines* Ventricular Function, Left Ventricular Pressure |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Isoquinolines; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 0/Tetrahydroisoquinolines; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 56-65-5/Adenosine Triphosphate; 58-82-2/Bradykinin; 67-07-2/Phosphocreatine; 82768-85-2/quinaprilat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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