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Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats
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SYSNO ASEP 0504092 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats Author(s) Hrdlička, Jaroslav (FGU-C) ORCID, RID
Neckář, Jan (FGU-C) RID, ORCID
Papoušek, František (FGU-C)
Husková, Z. (CZ)
Kikerlová, S. (CZ)
Vaňourková, Z. (CZ)
Vernerová, Z. (CZ)
Akat, Firat (FGU-C)
Vašinová, Jana (FGU-C)
Hammock, B.D. (US)
Hwang, S.H. (US)
Imig, J. D. (US)
Falck, J. R. (US)
Červenka, L. (CZ)
Kolář, František (FGU-C) RID, ORCID, SAIArticle number 159 Source Title Frontiers in Pharmacology. - : Frontiers Media - ISSN 1663-9812
Roč. 10, Mar 1 (2019)Number of pages 12 s. Language eng - English Country CH - Switzerland Keywords epoxyeicosatrienoic acid ; soluble epoxide hydrolase ; chronic heart failure ; hypertension ; myocardial infarction ; echocardiography Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects NV15-27735A GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000459963300001 DOI 10.3389/fphar.2019.00159 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2020 Electronic address https://doi.org/10.3389/fphar.2019.00159
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