Effect of Angiotensin-Converting Enzyme Blockade, Alone or Combined With Blockade of Soluble Epoxide Hydrolase, on the Course of Congestive Heart Failure and Occurrence of Renal Dysfunction in Ren-2 Transgenic Hypertensive Rats With Aorto-Caval Fistula
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Physiological Research (20pkt w roku publikacji)
ISSN
0862-8408
EISSN
Wydawca
ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY
DOI
URL
Rok publikacji
2018
Numer zeszytu
3
Strony od-do
401-415
Numer tomu
67
Identyfikator DOI
Liczba arkuszy
1,17
Słowa kluczowe
en
Congestive heart failure
Renal dysfunction
Hypertension
Aorto-caval fistula
Epoxyeicosatrienoic acids
Soluble epoxide hydrolase
Renin-angiotensin system
Open access
Tryb otwartego dostępu
Inne
Wersja tekstu w otwartym dostępie
Wersja opublikowana
Licencja otwartego dostępu
Creative Commons — Uznanie autorstwa
Czas opublikowania w otwartym dostępie
Razem z publikacją
Data udostępnienia w sposób otwarty
Streszczenia
Język
en
Treść
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 \% but increased to 41 \% after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/I). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 \% at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 \%). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.
Cechy publikacji
discipline:Medycyna
discipline:Medicine
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:874312