| Levosimendan improves cardiac function and survival in rats with angiotensin II-induced hypertensive heart failure. | |
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MedLine Citation:
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PMID: 20811386 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcium-sensitizing agents improve cardiac function in acute heart failure; however, their long-term effects on cardiovascular mortality are unknown. We tested the hypothesis that levosimendan, an inodilator that acts through calcium sensitization, opening of ATP-dependent potassium channels and phosphodiesterase III inhibition, improves cardiac function and survival in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin II (Ang II)-induced hypertensive heart failure. Levosimendan (1 mg kg(-1)) was administered orally to 4-week-old dTGRs and normotensive Sprague-Dawley rats for 4 weeks. Untreated dTGRs developed severe hypertension, cardiac hypertrophy, heart failure with impaired diastolic relaxation, and exhibited a high mortality rate at the age of 8 weeks. Levosimendan did not decrease blood pressure and did not prevent cardiac hypertrophy. However, levosimendan improved systolic function, decreased cardiac atrial natriuretic peptide mRNA expression, ameliorated Ang II-induced cardiac damage and decreased mortality. Levosimendan did not correct Ang II-induced diastolic dysfunction and did not influence heart rate. In a separate survival study, levosimendan increased dTGR survival by 58% and median survival time by 27% (P=0.004). Our findings suggest that levosimendan ameliorates Ang II-induced hypertensive heart failure and reduces mortality. The results also support the notion that the effects of levosimendan in dTGRs are mediated by blood pressure-independent mechanisms and include improved systolic function and amelioration of Ang II-induced coronary and cardiomyocyte damage. |
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Authors:
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Agnieszka Biala; Essi Martonen; Petri Kaheinen; Jouko Levijoki; Piet Finckenberg; Saara Merasto; Marjut Louhelainen; Dominik N Muller; Friedrich C Luft; Eero Mervaala |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-02 |
Journal Detail:
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Title: Hypertension research : official journal of the Japanese Society of Hypertension Volume: 33 ISSN: 1348-4214 ISO Abbreviation: Hypertens. Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2011-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9307690 Medline TA: Hypertens Res Country: England |
Other Details:
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Languages: eng Pagination: 1004-11 Citation Subset: IM |
Affiliation:
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Institute of Biomedioine, University of Helsinki, Helsinki, Finland. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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adverse effects*,
metabolism Angiotensinogen / genetics, metabolism Animals Blood Pressure / drug effects, physiology Cardiotonic Agents / pharmacology, therapeutic use Disease Models, Animal Heart / drug effects, physiology* Heart Failure / drug therapy*, physiopathology Heart Rate / drug effects, physiology Humans Hydrazones / pharmacology, therapeutic use* Hypertension / drug therapy*, metabolism, physiopathology Major Histocompatibility Complex / physiology Male Pyridazines / pharmacology, therapeutic use* Rats Rats, Sprague-Dawley Rats, Transgenic Renin / genetics, metabolism Renin-Angiotensin System / drug effects, physiology Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Hydrazones; 0/Pyridazines; 0/bcl-2-Associated X Protein; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 131741-08-7/simendan; EC 3.4.23.15/Renin; EC 3.6.3.8/Atp2a2 protein, rat; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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