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Matrix metalloproteinase 9/neutrophil gelatinase associated lipocalin/tissue inhibitor of metalloproteinases 1 complexes are localized within cardiomyocytes and serve as a reservoir of active metalloproteinases in porcine female myocardium

100%

Kiczak L., Tomaszek A., Bania J., Paslawska U., Zacharski M., Janiszewski A., Rybinska I., Dziegiel P., von Haehling S., Ardehali H., Jankowska E. A., Ponikowski P.

Journal of Physiology and Pharmacology

2014

tom 65

nr 3

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

80%

Louhelainen M., Merasto S., Finckenberg P., Vahtola E., Kaheinen P., Leskinen H., Levijoki J., Pollesello P., Haikala H., Mervaala E. M. A.

Journal of Physiology and Pharmacology

2009

tom 60

nr 3

41-47

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.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

1 Ardehali H.

1 Bania J.

1 Dziegiel P.

1 Finckenberg P.

1 Haikala H.

1 Janiszewski A.

1 Jankowska E. A.

1 Kaheinen P.

1 Kiczak L.

1 Leskinen H.

1 Levijoki J.

1 Louhelainen M.

1 Merasto S.

1 Mervaala E. M. A.

1 Paslawska U.

1 Pollesello P.

1 Ponikowski P.

1 Rybinska I.

1 Tomaszek A.

1 Vahtola E.

1 Zacharski M.

1 von Haehling S.

1 2014

1 2009

Wyniki wyszukiwania

Matrix metalloproteinase 9/neutrophil gelatinase associated lipocalin/tissue inhibitor of metalloproteinases 1 complexes are localized within cardiomyocytes and serve as a reservoir of active metalloproteinases in porcine female myocardium

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