Epoxyeicosatrienoic acid analog attenuates the development of malignant hypertension, but does not reverse it once established: a study in Cyp1a1-Ren-2 transgenic rats

0462469 - FGÚ 2017 RIV GB eng J - Journal Article
Jíchová, Š. - Kopkan, L. - Husková, Z. - Doleželová, Š. - Neckář, Jan - Kujal, P. - Vernerová, Z. - Kramer, H. J. - Sadowski, J. - Kompanowska - Jezierska, E. - Reddy, N. R. - Falck, J. R. - Imig, J. D. - Červenka, L.
Epoxyeicosatrienoic acid analog attenuates the development of malignant hypertension, but does not reverse it once established: a study in Cyp1a1-Ren-2 transgenic rats.
Journal of Hypertension. Roč. 34, č. 10 (2016), s. 2008-2025. ISSN 0263-6352. E-ISSN 1473-5598
R&D Projects: GA ČR(CZ) GA15-07544S
Institutional support: RVO:67985823
Keywords : epoxyeicosatrienoic acid analog * malignant hypertension * renal blood flow autoregulation * renin-angiotensin system * sodium excretion
Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery
Impact factor: 4.085, year: 2016

We evaluated the therapeutic effectiveness of a new, orally active epoxyeicosatrienoic acid analog (EET-A) in rats with angiotensin II (ANG II)-dependent malignant hypertension. Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C). EET-A treatment was started either simultaneously with I3C induction process or 10 days later during established hypertension. Blood pressure (BP), indices of renal and cardiac injury, and plasma and kidney levels of the components of the renin-angiotensin system (RAS) were determined. In I3C-induced hypertensive rats, early EET-A treatment attenuated BP increase (to 175 ± 3 vs. 193 ± 4 mmHg, on day 13), reduced albuminuria (15 ± 1 vs. 28 ± 2 mg/24 h), and cardiac hypertrophy as compared with untreated I3C-induced rats. This was associated with suppression of plasma and kidney ANG II levels and increases in plasma and kidney angiotensin (1-7) concentrations Remarkably, late EET-A treatment did not lower BP or improve renal and cardiac injury; indices of RAS activity were not affected. The new, orally active EET-A attenuated the development of experimental ANG II-dependent malignant hypertension, likely via suppression of the hypertensiogenic axis and augmentation of the vasodilatory/natriuretic axis of RAS.
Permanent Link: http://hdl.handle.net/11104/0261933