1. Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension
- Author
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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, and Neckář, Jan
- Subjects
Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease ,Kidney Disease ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Hypertension ,Albuminuria ,Angiotensin II ,Animals ,Antihypertensive Agents ,Arachidonic Acids ,Arrhythmias ,Cardiac ,Blood Pressure ,Rats ,Rats ,Sprague-Dawley ,Rats ,Transgenic ,epoxyeicosatrienoic acid analogue ,epoxyeicosatrienoic acid ,hypertension ,infarct size ,ischemic arrhythmia ,kidney ,renin-angiotensin system ,soluble epoxide hydrolase inhibitor ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
ObjectiveWe 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.MethodsRen-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.ResultsTreatment 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.ConclusionThe 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.
- Published
- 2018