20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F18%3A00077394" target="_blank" >RIV/00023001:_____/18:00077394 - isvavai.cz</a>

Result on the web

<a href="http://www.bioscirep.org/content/38/5/BSR20171496" target="_blank" >http://www.bioscirep.org/content/38/5/BSR20171496</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/BSR20171496" target="_blank" >10.1042/BSR20171496</a>

Result language

angličtina

Original language name

20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats

Original language description

We hypothesized that vascular actions of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of cytochrome P450 (CYP450)-dependent omega-hydroxylase, potentiate prohypertensive actions of angiotensin II (ANG II) in Cyp1a1-Ren-2 transgenic rats, a model of ANG II-dependent malignant hypertension. Therefore, we evaluated the antihypertensive effectiveness of 20-HETE receptor antagonist (AAA) in this model. Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C), a natural xenobiotic. Treatment with AAA was started either simultaneously with induction of hypertension or 10 days later, during established hypertension. Systolic blood pressure (SBP) was monitored by radiotelemetry, indices of renal and cardiac injury, and kidney ANG II levels were determined. In I3C-induced hypertensive rats, early AAA treatment reduced SBP elevation (to 161 +/- 3 compared with 199 +/- 3 mmHg in untreated I3C-induced rats), reduced albuminuria, glomerulosclerosis index, and cardiac hypertrophy (P&lt;0.05 in all cases). Untreated I3C-induced rats showed augmented kidney ANG II (405 +/- 14 compared with 52 +/- 3 fmol/g in non-induced rats, P&lt;0.05) which was markedly lowered by AAA treatment (72 +/- 6 fmol/g). Remarkably, in TGR with established hypertension, AAA also decreased SBP (from 187 +/- 4 to 158 +/- 4 mmHg, P&lt;0.05) and exhibited organoprotective effects in addition to marked suppression of kidney ANG II levels. In conclusion, 20-HETE antagonist attenuated the development and largely reversed the established ANG II-dependent malignant hypertension, likely via suppression of intrarenal ANG II levels. This suggests that intrarenal ANG II activation by 20-HETE is important in the pathophysiology of this hypertension form.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NV15-25396A" target="_blank" >NV15-25396A: Central and peripheral modulation of vascular tone and sodium excretion: the role of brain and kidney in pathophysiology of hypertension</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioscience reports [online]

ISSN

1573-4935

e-ISSN

—

Volume of the periodical

38

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

"art. no. BSR20171496"

UT code for WoS article

000448897800005

EID of the result in the Scopus database

2-s2.0-85053116578