Levosimendan improves cardiac function and survival in rats with angiotensin II-induced hypertensive heart failure

Item Type:	Article
Title:	Levosimendan improves cardiac function and survival in rats with angiotensin II-induced hypertensive heart failure
Creators Name:	Biala, A. and Martonen, E. and Kaheinen, P. and Levijoki, J. and Finckenberg, P. and Merasto, S. and Louhelainen, M. and Mueller, D.N. and Luft, F.C. and Mervaala, E.
Abstract:	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.
Keywords:	Angiotensin II, Calcium Sensitizers, Heart Failure, Hypertrophy, Animals, Rats
Source:	Hypertension Research
ISSN:	0916-9636
Publisher:	Nature Publishing Group
Volume:	33
Number:	10
Page Range:	1004-1011
Date:	October 2010
Official Publication:	https://doi.org/10.1038/hr.2010.123
PubMed:	View item in PubMed

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