Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension. Issue 6 (June 2018)

• Record Type: Journal Article
• Authors: Červenka, Luděk; Husková, Zuzana; Kopkan, Libor; Kikerlová, Soňa; Sedláková, Lenka; Vaňourková, Zdenka; Alánová, Petra; Kolář, František; Hammock, Bruce D.; Hwang, Sung H.; Imig, John D.; Falck, John R.; Sadowski, Janusz; Kompanowska-Jezierska, Elzbieta; Neckář, Jan
• Is Part Of: Journal of hypertension. Volume 36:Issue 6(2018:Jun.)
• Publication Date: 2018-06
• Subjects: epoxyeicosatrienoic acid analogue -- epoxyeicosatrienoic acid -- hypertension -- infarct size -- ischemic arrhythmia -- kidney -- renin–angiotensin system -- soluble epoxide hydrolase inhibitor; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000001708
• Languages: English
• ISSNs: 1473-5598

Abstract

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. Abstract : Supplemental Digital Content is available in the text