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Cardiovascular effects of the combination of levosimendan and valsartan in hypertensive Dahl/Rapp rats.
J Physiol Pharmacol. 2011 Jun; 62(3):275-85.JP

Abstract

Hypertension is the main risk factor for left ventricular hypertrophy and development of diastolic heart failure. There is no yet treatment, which can effectively reduce mortality in patients suffering from heart failure with preserved systolic function. We tested whether the calcium sensitizer levosimendan and the AT1-receptor antagonist valsartan could protect from salt-induced hypertension, cardiovascular mortality and heart failure in Dahl/Rapp salt-sensitive rats fed for 7 weeks with a high salt diet (8% NaCl). Levosimendan (1 mg/kg/day via drinking water) and valsartan (30 mg/kg in the food) monotherapies and their combination prevented mortality in Dahl/Rapp rats. The drug combination evoked an additive effect on blood pressure, cardiac hypertrophy, cardiomyocyte cross-sectional area, target organ damage and myocardial ANP mRNA expression. There was a close correlation between systolic blood pressure and cardiac hypertrophy, cardiac and renal damage. As compared to Dahl/Rapp controls kept on low-salt diet (NaCl 0.3%). The high salt rats exhibited impaired diastolic relaxation as assessed by isovolumic relaxation time. Levosimendan alone and in combination with valsartan, improved diastolic relaxation without significantly improving systolic function. Our findings are evidence for an additive effect between levosimendan and valsartan on blood pressure and a blood pressure-dependent protection against the development of salt-induced target organ damage. The present study also demonstrates that levosimendan, alone or in combination with valsartan, can correct diastolic dysfunction induced by salt-dependent hypertension.

Authors+Show Affiliations

Institute of Biomedicine, University of Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21893687

Citation

Biala, A, et al. "Cardiovascular Effects of the Combination of Levosimendan and Valsartan in Hypertensive Dahl/Rapp Rats." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 62, no. 3, 2011, pp. 275-85.
Biala A, Finckenberg P, Korpi A, et al. Cardiovascular effects of the combination of levosimendan and valsartan in hypertensive Dahl/Rapp rats. J Physiol Pharmacol. 2011;62(3):275-85.
Biala, A., Finckenberg, P., Korpi, A., Loytainen, M., Martonen, E., Levijoki, J., & Mervaala, E. (2011). Cardiovascular effects of the combination of levosimendan and valsartan in hypertensive Dahl/Rapp rats. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 62(3), 275-85.
Biala A, et al. Cardiovascular Effects of the Combination of Levosimendan and Valsartan in Hypertensive Dahl/Rapp Rats. J Physiol Pharmacol. 2011;62(3):275-85. PubMed PMID: 21893687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular effects of the combination of levosimendan and valsartan in hypertensive Dahl/Rapp rats. AU - Biala,A, AU - Finckenberg,P, AU - Korpi,A, AU - Loytainen,M, AU - Martonen,E, AU - Levijoki,J, AU - Mervaala,E, PY - 2011/01/27/received PY - 2011/06/28/accepted PY - 2011/9/7/entrez PY - 2011/9/7/pubmed PY - 2012/3/17/medline SP - 275 EP - 85 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J. Physiol. Pharmacol. VL - 62 IS - 3 N2 - Hypertension is the main risk factor for left ventricular hypertrophy and development of diastolic heart failure. There is no yet treatment, which can effectively reduce mortality in patients suffering from heart failure with preserved systolic function. We tested whether the calcium sensitizer levosimendan and the AT1-receptor antagonist valsartan could protect from salt-induced hypertension, cardiovascular mortality and heart failure in Dahl/Rapp salt-sensitive rats fed for 7 weeks with a high salt diet (8% NaCl). Levosimendan (1 mg/kg/day via drinking water) and valsartan (30 mg/kg in the food) monotherapies and their combination prevented mortality in Dahl/Rapp rats. The drug combination evoked an additive effect on blood pressure, cardiac hypertrophy, cardiomyocyte cross-sectional area, target organ damage and myocardial ANP mRNA expression. There was a close correlation between systolic blood pressure and cardiac hypertrophy, cardiac and renal damage. As compared to Dahl/Rapp controls kept on low-salt diet (NaCl 0.3%). The high salt rats exhibited impaired diastolic relaxation as assessed by isovolumic relaxation time. Levosimendan alone and in combination with valsartan, improved diastolic relaxation without significantly improving systolic function. Our findings are evidence for an additive effect between levosimendan and valsartan on blood pressure and a blood pressure-dependent protection against the development of salt-induced target organ damage. The present study also demonstrates that levosimendan, alone or in combination with valsartan, can correct diastolic dysfunction induced by salt-dependent hypertension. SN - 1899-1505 UR - https://www.unboundmedicine.com/medline/citation/21893687/Cardiovascular_effects_of_the_combination_of_levosimendan_and_valsartan_in_hypertensive_Dahl/Rapp_rats_ L2 - http://www.jpp.krakow.pl/journal/archive/06_11/pdf/275_06_11_article.pdf DB - PRIME DP - Unbound Medicine ER -