RGD Reference Report - Effects of calcium sensitizer OR-1986 on a cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats. - Rat Genome Database

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Effects of calcium sensitizer OR-1986 on a cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats.

Authors: Louhelainen, M  Merasto, S  Finckenberg, P  Vahtola, E  Kaheinen, P  Leskinen, H  Levijoki, J  Pollesello, P  Haikala, H  Mervaala, EM 
Citation: Louhelainen M, etal., J Physiol Pharmacol. 2009 Sep;60(3):41-7.
RGD ID: 11252108
Pubmed: PMID:19826180   (View Abstract at PubMed)

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 p16(INK4a) 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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdkn2aRatresponse to salt stress  IEP  RGD 
Cdkn2a_v1Ratresponse to salt stress  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)
Cdkn2a_v1  (cyclin-dependent kinase inhibitor 2A, variant 1)


Additional Information