Effects of epoxyeicosatrienoic acid-enhancing therapy on the course of congestive heart failure in angiotensin ii-dependent rat hypertension: From mrna analysis towards functional in vivo evaluation

Petr Kala, Matúš Miklovič, Šárka Jíchová, Petra Škaroupková, Zdeňka Vaňourková, Hana Maxová, Olga Gawrys, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, John D. Imig, John R. Falck, Josef Veselka, Luděk Červenka, Renáta Aiglová, Marek Vícha, Vít Gloger, Miloš Táborský

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

This study evaluates the effects of chronic treatment with EET-A, an orally active epoxye-icosatrienoic acid (EETs) analog, on the course of aorto-caval fistula (ACF)-induced heart failure (HF) in Ren-2 transgenic rats (TGR), a model characterized by hypertension and augmented activity of the renin-angiotensin system (RAS). The results were compared with standard pharmacological blockade of the RAS using angiotensin-converting enzyme inhibitor (ACEi). The rationale for employing EET-A as a new treatment approach is based on our findings that apart from increased RAS activity, untreated ACF TGR also shows kidney and left ventricle (LV) tissue deficiency of EETs. Untreated ACF TGR began to die 17 days after creating ACF and were all dead by day 84. The treatment with EET-A alone or ACEi alone improved the survival rate: in 156 days after ACF creation, it was 45.5% and 59.4%, respectively. The combined treatment with EET-A and ACEi appeared to improve the final survival to 71%; however, the difference from either single treatment regimen did not reach significance. Nevertheless, our findings support the notion that targeting the cytochrome P-450-dependent epoxygenase pathway of arachidonic acid metabolism should be considered for the treatment of HF.

Original languageEnglish (US)
Article number1053
JournalBiomedicines
Volume9
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Angiotensin-converting enzyme inhibitor
  • Aorto-caval fistula
  • Congestive heart failure
  • Cytochrome P-450
  • Epoxyeicosatrienoic acids
  • Hyperten-sion
  • Ren-2 transgenic rats
  • Renin-angiotensin system
  • Volume-overload heart failure

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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