Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension

0489812 - FGÚ 2019 RIV GB eng J - Journal Article
Červenka, L. - Husková, Z. - Kopkan, L. - Kikerlová, S. - Sedláková, L. - Vaňourková, Z. - Alánová, Petra - Kolář, František - Hammock, B.D. - Hwang, S.H. - Imig, J. D. - Falck, J. R. - Sadowski, J. - Kompanowska - Jezierska, E. - Neckář, Jan
Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension.
Journal of Hypertension. Roč. 36, č. 6 (2018), s. 1326-1341. ISSN 0263-6352. E-ISSN 1473-5598
R&D Projects: GA ČR(CZ) GA15-07544S
Institutional support: RVO:67985823
Keywords : epoxyeicosatrienoic acid analogue * epoxyeicosatrienoic acid * infarct size * ischemic arrhythmia * kidney * renin–angiotensin system * soluble epoxide hydrolase inhibitor
OECD category: Physiology (including cytology)
Impact factor: 4.209, year: 2018

We examined the effects of treatment with soluble epoxide hydrolase inhibitor (sEHi) and epoxyeicosatrienoic acids (EETs) analogue (EET-A), given alone or combined, on blood pressure (BP) and ischemia/reperfusion myocardial injury in rats with angiotensin II (ANG II)-dependent hypertension.Ren-2 transgenic rats (TGR) were used as a model of ANG II-dependent hypertension and Hannover Sprague–Dawley rats served as controls. Rats were treated for 14 days with sEHi or EET-A and BP was measured by radiotelemetry. Albuminuria, cardiac hypertrophy and concentrations of ANG II and EETs were determined. Separate groups were subjected to acute myocardial ischemia/reperfusion injury and the infarct size and ventricular arrhythmias were determined.Treatment of TGR with sEHi and EET-A, given alone or combined, decreased BP to a similar degree, reduced albuminuria and cardiac hypertrophy to similar extent, only treatment regimens including sEHi increased myocardial and renal tissue concentrations of EETs. sEHi and EET-A, given alone or combined, suppressed kidney ANG II levels in TGR. Remarkably, infarct size did not significantly differ between TGR and Hannover Sprague–Dawley rats, but the incidence of ischemia-induced ventricular fibrillations was higher in TGR. Application of sEHi and EET-A given alone and combined sEHi and EET-A treatment were all equally effective in reducing life-threatening ventricular fibrillation in TGR.The findings indicate that chronic treatment with either sEHi or EET-A exerts distinct antihypertensive and antiarrhythmic actions in our ANG II-dependent model of hypertension whereas combined administration of sEHi and EET-A does not provide additive antihypertensive or cardioprotective effects.
Permanent Link: http://hdl.handle.net/11104/0284155