| Effects of the calcium sensitizer OR-1896, a metabolite of levosimendan, on post-infarct heart failure and cardiac remodelling in diabetic Goto-Kakizaki rats. | |
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MedLine Citation:
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PMID: 20412071 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Levosimendan is a novel, short half-life calcium sensitizer used as pharmacological inotropic support in acute decompensated heart failure. After oral administration, levosimendan is metabolized to OR-1855, which, in rats, is further metabolized into OR-1896. OR-1896 is a long-lasting metabolite of levosimendan sharing the pharmacological properties of the parent compound. EXPERIMENTAL APPROACH: Effects of oral OR-1896 treatment on post-infarct heart failure and cardiac remodelling were assessed in diabetic Goto-Kakizaki (GK) rats, an animal model of type II diabetes. Myocardial infarction (MI) was produced to GK rats by coronary ligation. Twenty-four hours after MI or sham operation, the rats were randomized into four groups: (i) MI; (ii) MI + OR-1896 treatment; (iii) sham; and (iv) sham + OR-1896. Cardiac function and markers of cardiac remodelling were assessed 1, 4 and 12 weeks after MI. KEY RESULTS: OR-1896 increased ejection fraction and fractional shortening in GK rats with MI. OR-1896 ameliorated post-infarct cardiac hypertrophy, and prevented the MI-induced increase in cardiac mRNA for atrial natriuretic peptide, monocyte chemoattractant protein-1 and connective tissue growth factor, markers of pressure/volume overload, inflammation and fibrosis respectively. OR-1896 also suppressed mRNA for senescence-associated p16(INK4A) and p19(ARF). The beneficial effects of OR-1896 were more prominent at week 12 than at week 4. OR-1896 did not influence systolic blood pressure, blood glucose level, myocardial infarct size or cardiovascular mortality. CONCLUSIONS AND IMPLICATIONS: Oral treatment with calcium sensitizer OR-1896 protects against post-infarct heart failure and cardiac remodelling in experimental model of type II diabetes. |
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Authors:
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Marjut Louhelainen; Saara Merasto; Piet Finckenberg; Erik Vahtola; Petri Kaheinen; Jouko Levijoki; Eero Mervaala |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 160 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-23 Completed Date: 2010-07-26 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 142-52 Citation Subset: IM |
Affiliation:
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Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetamides
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pharmacology*,
therapeutic use Animals Biological Markers / metabolism Cardiac Volume / drug effects Cell Aging Diabetes Mellitus, Type 2 / complications, drug therapy*, physiopathology Fibrosis Heart Failure / drug therapy*, etiology, physiopathology Inflammation / metabolism Mitochondria, Heart / metabolism Myocardial Infarction / etiology*, pathology, physiopathology Myocytes, Cardiac / drug effects, pathology Pyridazines / pharmacology*, therapeutic use Random Allocation Rats Tetrazoles / therapeutic use Time Factors Valine / analogs & derivatives, therapeutic use Vasodilator Agents / therapeutic use Ventricular Pressure / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Acetamides; 0/Biological Markers; 0/N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide; 0/Pyridazines; 0/Tetrazoles; 0/Vasodilator Agents; 137862-53-4/valsartan; 7004-03-7/Valine |
| Comments/Corrections | |
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