Journal
JOURNAL OF HYPERTENSION
Volume 36, Issue 6, Pages 1326-1341Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000001708
Keywords
epoxyeicosatrienoic acid analogue; epoxyeicosatrienoic acid; hypertension; infarct size; ischemic arrhythmia; kidney; renin-angiotensin system; soluble epoxide hydrolase inhibitor
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Funding
- Czech Science Foundation (GACR) [15-07544S]
- Robert A. Welch Foundation [I-001]
- National Institute of Health (NIH) grant [DK103616]
- Dr Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee grant
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P42ES004699, R01ES002710] Funding Source: NIH RePORTER
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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.
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