| Eplerenone improves vascular function and reduces platelet activation in diabetic rats. | |
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MedLine Citation:
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PMID: 20228414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diabetes is associated with endothelial dysfunction and platelet activation, both of which contribute to increased cardiovascular risk. We investigated whether the selective mineralocorticoid receptor (MR) antagonist eplerenone improves endothelial dysfunction and reduces platelet activation in diabetic rats. Male Wistar-rats were injected with streptozotocin (50 mg/kg i.v.) to induce insulin-deficient diabetes. After 2 weeks, treatment with eplerenone (100 mg/kg/day) or vehicle was initiated for 2 weeks. Aortic superoxide production determined by lucigenin-enhanced chemiluminescence and 2-hydroxyethidium formation was significantly increased in rats with diabetes and reduced by treatment with eplerenone (chemiluminescence: control 2045+/-227, STZ-placebo 3977+/-340, p<0.05 vs. control, STZ-eplerenone 1762+/-307, p<0.05 vs. STZ-placebo). Endothelium-dependent vasorelaxation was significantly attenuated in diabetic rats and was normalized by eplerenone (maximum relaxation in % of precontraction: control 95+/-3, STZ-placebo 82+/-3, p<0.01 vs. control, STZ-eplerenone 99+/-1, p<0.01 vs. STZ-placebo). Treatment with the selective MR antagonist significantly reduced fibrinogen-binding on activated GPIIb/IIIa (immunofluorescence: control 161+/-7, STZ-placebo 208+/-16, p<0.05 vs. control, STZ-eplerenone 173+/-6, p<0.05 vs. STZ-placebo). Eplerenone improves endothelial function by reducing superoxide formation and increasing NO bioavailability in diabetic rats. Platelet activation was significantly reduced by eplerenone. Selective MR blockade may constitute a useful therapeutic approach for treatment of vascular dysfunction in diabetes. |
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Authors:
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A Schafer; C Vogt; D Fraccarollo; J Widder; U Flierl; S K Hildemann; G Ertl; J Bauersachs |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society Volume: 61 ISSN: 1899-1505 ISO Abbreviation: J. Physiol. Pharmacol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-03-15 Completed Date: 2010-10-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9114501 Medline TA: J Physiol Pharmacol Country: Poland |
Other Details:
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Languages: eng Pagination: 45-52 Citation Subset: IM |
Affiliation:
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Medizinische Klinik und Poliklinik I, Universitatsklinikum Wurzburg, Julius-Maximilians-Universitat Wurzburg, Wurzburg, Germany. a.schaefer@medizin.uni-wuerzburg.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Diabetes Mellitus, Experimental / drug therapy*, physiopathology Dose-Response Relationship, Drug Endothelium, Vascular / drug effects, physiology* Male Platelet Aggregation Inhibitors / pharmacology, therapeutic use* Rats Rats, Wistar Spironolactone / analogs & derivatives*, pharmacology, therapeutic use Vasodilation / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Platelet Aggregation Inhibitors; 0/eplerenone; 52-01-7/Spironolactone |
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