期刊
BIOMEDICINES
卷 9, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9081053
关键词
congestive heart failure; volume-overload heart failure; aorto-caval fistula; hypertension; Ren-2 transgenic rats; cytochrome P-450; epoxyeicosatrienoic acids; renin-angiotensin system; angiotensin-converting enzyme inhibitor
资金
- Ministry of Health of the Czech Republic [17-28220A]
- Grant Agency of Charles University [68121]
- 27 Robert A. Welch Foundation [I-0011]
- Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A.
The study showed that treatment with EET-A and ACEi improved survival rates in ACF TGR, but combined treatment did not significantly differ from single treatment regimens. Targeting the cytochrome P-450-dependent epoxygenase pathway of arachidonic acid metabolism may be considered for HF treatment.
This study evaluates the effects of chronic treatment with EET-A, an orally active epoxyeicosatrienoic 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.
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