Fenofibrate attenuates malignant hypertension by suppression of the renin-angiotensin system: 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_____%2F16%3A00060237" target="_blank" >RIV/00023001:_____/16:00060237 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10335793

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0002962916305006" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0002962916305006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.amjms.2016.09.008" target="_blank" >10.1016/j.amjms.2016.09.008</a>

Result language

angličtina

Original language name

Fenofibrate attenuates malignant hypertension by suppression of the renin-angiotensin system: a study in Cyp1a1-Ren-2 transgenic rats

Original language description

Background: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP) dependent omega-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II) dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. Methods: Malignant hypertension was induced by 12 days' dietary administration of 0.3 % indole-3-carbinol (I3C), a natural xenobiotic that activates a mouse renin gene. We hypothesized that chronic administration of fenofibrate, 190 mg/kg body weight, a lipid-lowering drug, should increase renal production of 20-HETE, a tubular transport inhibitor; an expected increase in sodium excretion would oppose the development of ANG II dependent malignant hypertension. Blood pressure was monitored by radiotelemetry, and at the end of the experiment rats were prepared for renal functional studies to evaluate in vivo the pressure-natriuresis relationship in response to stepwise reductions in renal arterial pressure (RAP). Results: In I3C-induced rats, the treatment with fenofibrate significantly attenuated hypertension and improved the slope of the pressure-natriuresis relationship. Although fenofibrate treatment increased kidney gene and protein expression of CYP4A1, a major isoform responsible for 20-HETE formation, it did not increase renal 20-HETE concentration. On the contrary, fenofibrate treatment significantly suppressed renin gene expression, plasma renin activity and plasma and kidney ANG II levels. Conclusions: Fenofibrate treatment significantly attenuated the course of malignant hypertension in I3C-induced CYP1a1Ren-2 transgenic rats, and the mechanism responsible for antihypertensive action was fenofibrate-induced suppression of renin-angiotensin system activity.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FA - Cardiovascular diseases including cardio-surgery

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

American journal of the medical sciences

ISSN

0002-9629

e-ISSN

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Volume of the periodical

352

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

618-630

UT code for WoS article

000392736700012

EID of the result in the Scopus database

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