TY - JOUR
T1 - Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension
AU - Červenka, Luděk
AU - Husková, Zuzana
AU - Kopkan, Libor
AU - Kikerlová, Soňa
AU - Sedláková, Lenka
AU - Vaňourková, Zdenka
AU - Alánová, Petra
AU - Kolář, František
AU - Hammock, Bruce D.
AU - Hwang, Sung H.
AU - Imig, John D.
AU - Falck, John R.
AU - Sadowski, Janusz
AU - Kompanowska-Jezierska, Elzbieta
AU - Neckář, Jan
N1 - Funding Information:
This study was primarily supported by grant no. 15-07544S awarded to Z.H. by the Czech Science Foundation (GACˇ R). J.R.F. was supported in part by the Robert A. Welch Foundation (I-001). J.D.I. and this work was partially supported by a National Institute of Health (NIH) grant (DK103616) and a Dr Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee grant.
Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
KW - epoxyeicosatrienoic acid
KW - epoxyeicosatrienoic acid analogue
KW - hypertension
KW - infarct size
KW - ischemic arrhythmia
KW - kidney
KW - renin-angiotensin system
KW - soluble epoxide hydrolase inhibitor
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U2 - 10.1097/HJH.0000000000001708
DO - 10.1097/HJH.0000000000001708
M3 - Article
C2 - 29570510
AN - SCOPUS:85046619324
SN - 0263-6352
VL - 36
SP - 1326
EP - 1341
JO - Journal of hypertension
JF - Journal of hypertension
IS - 6
ER -