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

Luděk Červenka, Zuzana Husková, Libor Kopkan, Soňa Kikerlová, Lenka Sedláková, Zdenka Vaňourková, Petra Alánová, František Kolář, Bruce D. Hammock, Sung H. Hwang, John D. Imig, John R. Falck, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Jan Neckář

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1326-1341
Number of pages16
JournalJournal of hypertension
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2018

Keywords

  • epoxyeicosatrienoic acid
  • epoxyeicosatrienoic acid analogue
  • hypertension
  • infarct size
  • ischemic arrhythmia
  • kidney
  • renin-angiotensin system
  • soluble epoxide hydrolase inhibitor

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension'. Together they form a unique fingerprint.

  • Cite this

    Červenka, L., Husková, Z., Kopkan, L., Kikerlová, S., Sedláková, L., Vaňourková, Z., Alánová, P., Kolář, F., Hammock, B. D., Hwang, S. H., Imig, J. D., Falck, J. R., Sadowski, J., Kompanowska-Jezierska, E., & Neckář, J. (2018). 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, 36(6), 1326-1341. https://doi.org/10.1097/HJH.0000000000001708