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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10376816" target="_blank" >RIV/00216208:11130/18:10376816 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023001:_____/18:00077079

Výsledek na webu

<a href="http://www.biomed.cas.cz/physiolres/pdf/67/67_401.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/67/67_401.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/NV17-28220A" target="_blank" >NV17-28220A: Farmakologické zásahy do metabolické cesty cytochromu P-450 jako nový přístup pro léčbu chronického srdečního selhání</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

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Svazek periodika

67

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

15

Strana od-do

401-415

Kód UT WoS článku

000439466000005

EID výsledku v databázi Scopus

2-s2.0-85050353397