Effects of calcium sensitizer OR-1896 on cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats

• Autorzy: Louhelainen M. , Merasto S. , Finckenberg P. , Vahtola E. , Kaheinen P. , Leskinen H. , Levijoki J. , Pollesello P. , Haikala H. , Mervaala E.M.A.
• Języki publikacji: EN

Abstrakty

EN

Calcium-sensitizing agents have been shown to improve cardiac function in patients suffering from acute decompensated heart failure, however, their long-term effects on cardiac remodeling and cardiovascular mortality are still largely unknown. In the present study we tested the hypothesis whether OR-1896, an active and long-lasting metabolite of calcium sensitizer levosimendan, prevents cardiovascular mortality and hypertension-induced myocardial remodelling in salt-sensitive Dahl/Rapp rats. OR-1896 was given orally to Dahl/Rapp SS rats on high-salt diet (NaCl 7% w/w) for 7 weeks at two different doses (0.5 and 0.05 mg/kg). OR-1896 prevented salt-induced cardiovascular mortality (survival rate 75 % in OR-1896 treated groups vs 38 % in untreated controls, p<0.01), ameliorated cardiac hypertrophy and improved systolic functions of the heart without major influence on systemic blood pressure. OR-1896 also ameliorated salt-induced increase in cardiac ANP mRNA expression and plasma BNP level. Salt-induced cardiac remodelling was associated with 4-fold increase in cardiac p16INK4a mRNA expression, a marker of cellular senescence. OR-1896 dose-dependently ameliorated cardiomyocyte senescence. Our findings suggest a therapeutic role for OR-1896 in the prevention of cardiac remodelling in salt-sensitive forms of hypertension. The present study also underscores the importance of cellular senescence in the pathogenesis of salt-induced hypertensive heart disease.

Słowa kluczowe

EN

calcium; cardiovascular mortality; myocardial remodelling; hypertension; rat; cardiac function; patient; heart failure; cardiac hypertrophy; blood pressure; mRNA expression; heart disease; senescence; myocardial infarction; cardiac remodelling

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2009
• Tom: 60
• Numer: 3
• Opis fizyczny: p.41-47,fig.,ref.

Twórcy

autor

Louhelainen M.

• University of Helsinki, Helsinki, P.O. BOX 63, FIN-00014, Finland

autor

Merasto S.

autor

Finckenberg P.

autor

Vahtola E.

autor

Kaheinen P.

autor

Leskinen H.

autor

Levijoki J.

autor

Pollesello P.

autor

Haikala H.

autor

Mervaala E.M.A.