Pharmacological blockade of soluble epoxide hydrolase attenuates the progression of congestive heart failure combined with chronic kidney disease: insights from studies with fawn-hooded hypertensive rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00077642" target="_blank" >RIV/00023001:_____/19:00077642 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10394225 RIV/00216208:11310/19:10394225 RIV/61989592:15110/19:73599985 RIV/00098892:_____/19:N0000124

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fphar.2019.00018/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fphar.2019.00018/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2019.00018" target="_blank" >10.3389/fphar.2019.00018</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacological blockade of soluble epoxide hydrolase attenuates the progression of congestive heart failure combined with chronic kidney disease: insights from studies with fawn-hooded hypertensive rats

Popis výsledku v původním jazyce

An association between congestive heart failure (CHF) and chronic kidney disease (CKD) results in extremely poor patient survival rates. Previous studies have shown that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, improves the survival rate in CHF induced by aorto-caval fistula (ACF) and attenuates CKD progression. This prompted us to examine if sEH inhibitor treatment would improve the outcome if both experimental conditions are combined. Fawn-hooded hypertensive (FHH) rats, a genetic model showing early CKD development was employed, and CHF was induced by ACF. Treatment with an sEH inhibitor was initiated 4 weeks after ACF creation, in FHH and in fawn-hooded low-pressure (FHL) rats, a control strain without renal damage. The follow-up period was 20 weeks. We found that ACF FHH rats exhibited substantially lower survival rates (all the animals died by week 14) as compared with the 64% survival rate observed in ACF FHL rats. The former group showed pronounced albuminuria (almost 30-fold higher than in FHL) and reduced intrarenal EET concentrations. The sEH inhibitor treatment improved survival rate and distinctly reduced increases in albuminuria in ACF FHH and in ACF FHL rats, however, all the beneficial actions were more pronounced in the hypertensive strain. These data indicate that pharmacological blockade of sEH could be a novel therapeutic approach for the treatment of CHF, particularly under conditions when it is associated with CKD.

Název v anglickém jazyce

Pharmacological blockade of soluble epoxide hydrolase attenuates the progression of congestive heart failure combined with chronic kidney disease: insights from studies with fawn-hooded hypertensive rats

Popis výsledku anglicky

An association between congestive heart failure (CHF) and chronic kidney disease (CKD) results in extremely poor patient survival rates. Previous studies have shown that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, improves the survival rate in CHF induced by aorto-caval fistula (ACF) and attenuates CKD progression. This prompted us to examine if sEH inhibitor treatment would improve the outcome if both experimental conditions are combined. Fawn-hooded hypertensive (FHH) rats, a genetic model showing early CKD development was employed, and CHF was induced by ACF. Treatment with an sEH inhibitor was initiated 4 weeks after ACF creation, in FHH and in fawn-hooded low-pressure (FHL) rats, a control strain without renal damage. The follow-up period was 20 weeks. We found that ACF FHH rats exhibited substantially lower survival rates (all the animals died by week 14) as compared with the 64% survival rate observed in ACF FHL rats. The former group showed pronounced albuminuria (almost 30-fold higher than in FHL) and reduced intrarenal EET concentrations. The sEH inhibitor treatment improved survival rate and distinctly reduced increases in albuminuria in ACF FHH and in ACF FHL rats, however, all the beneficial actions were more pronounced in the hypertensive strain. These data indicate that pharmacological blockade of sEH could be a novel therapeutic approach for the treatment of CHF, particularly under conditions when it is associated with CKD.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

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

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Frontiers in pharmacology [online]

ISSN

1663-9812

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

January 23

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

"art. no. 18"

Kód UT WoS článku

000456509000002

EID výsledku v databázi Scopus

2-s2.0-85064985153