Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00504092" target="_blank" >RIV/67985823:_____/19:00504092 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10404622 RIV/00023001:_____/19:00077699

Výsledek na webu

<a href="https://doi.org/10.3389/fphar.2019.00159" target="_blank" >https://doi.org/10.3389/fphar.2019.00159</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2019.00159" target="_blank" >10.3389/fphar.2019.00159</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats

Popis výsledku v původním jazyce

Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio-and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of postmyocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (Ped) and reduced fractional shortening (FS) and the peak rate of pressure development [C (dP/dt) max] in untreated HanSD compared to sham (non-MI) group [Ped: 30.5 +/- 3.3 vs. 9.7 +/- 1.3 mmHg, FS: 11.1 +/- 1.0 vs. 40.8 +/- 0.5%, C (dP/dt) max: 3890 +/- 291 vs. 5947 +/- 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [Ped: 19.4 +/- 2.2 mmHg, FS: 14.9 +/- 1.0%, C (dP/dt) max: 5278 +/- 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.

Název v anglickém jazyce

Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats

Popis výsledku anglicky

Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio-and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of postmyocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (Ped) and reduced fractional shortening (FS) and the peak rate of pressure development [C (dP/dt) max] in untreated HanSD compared to sham (non-MI) group [Ped: 30.5 +/- 3.3 vs. 9.7 +/- 1.3 mmHg, FS: 11.1 +/- 1.0 vs. 40.8 +/- 0.5%, C (dP/dt) max: 3890 +/- 291 vs. 5947 +/- 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [Ped: 19.4 +/- 2.2 mmHg, FS: 14.9 +/- 1.0%, C (dP/dt) max: 5278 +/- 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/NV15-27735A" target="_blank" >NV15-27735A: Rozvoj chronického srdečního selhání a kardiorenálního syndromu u hypertenzních potkanů po infarktu myokardu: úloha epoxyeikosatrienových kyselin.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

Mar 1

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

159

Kód UT WoS článku

000459963300001

EID výsledku v databázi Scopus

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