| Aldose reductase inhibition alone or combined with an adenosine A(3) agonist reduces ischemic myocardial injury. | |
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MedLine Citation:
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PMID: 11009428 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study investigated whether aldose reductase (AR) inhibition with zopolrestat, either alone or in combination with an adenosine A(3)-receptor agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion. Zopolrestat reduced infarct size by up to 61%, both in vitro (2 nM to 1 microM; EC(50) = 24 nM) and in vivo (50 mg/kg). Zopolrestat reduced myocardial sorbitol concentration (index of AR activity) by >50% (control, 15.0 +/- 2.2 nmol/g; 200 nM zopolrestat, 6.7 +/- 1.3 nmol/g). A modestly cardioprotective concentration of CB-MECA (0.2 nM) allowed a 50-fold reduction in zopolrestat concentration while providing a similar reduction in infarct size (infarct area/area at risk: control, 62 +/- 2%; 1 microM zopolrestat, 24 +/- 5%; 20 nM zopolrestat plus 0.2 nM CB-MECA, 20 +/- 4%). In conclusion, AR inhibition is cardioprotective both in vitro and in vivo. Furthermore, combining zopolrestat with an A(3) agonist allows a reduction in the zopolrestat concentration while maintaining an equivalent degree of cardioprotection. |
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Authors:
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W R Tracey; W P Magee; C A Ellery; J T MacAndrew; A H Smith; D R Knight; P J Oates |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 279 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2000 Oct |
Date Detail:
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Created Date: 2000-10-23 Completed Date: 2000-11-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: H1447-52 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular and Metabolic Diseases, Pfizer, Incorporated, Groton, Connecticut 06340, USA. w_ross_tracey@groton.pfizer.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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analogs & derivatives*,
pharmacology* Aldehyde Reductase / antagonists & inhibitors* Animals Benzothiazoles Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology* Male Myocardial Ischemia / pathology* Myocardium / metabolism, pathology Phthalazines / pharmacology* Rabbits Receptor, Adenosine A3 Receptors, Purinergic P1 / agonists* Sorbitol / metabolism Thiazoles / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Benzothiazoles; 0/CB MECA; 0/Enzyme Inhibitors; 0/Phthalazines; 0/Receptor, Adenosine A3; 0/Receptors, Purinergic P1; 0/Thiazoles; 110703-94-1/zopolrestat; 50-70-4/Sorbitol; 58-61-7/Adenosine; EC 1.1.1.21/Aldehyde Reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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