Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of 20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10360569" target="_blank" >RIV/00216208:11110/17:10360569 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/17:10360569 RIV/00023001:_____/17:00075971
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S000296291730215X" target="_blank" >http://www.sciencedirect.com/science/article/pii/S000296291730215X</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.amjms.2017.04.009" target="_blank" >10.1016/j.amjms.2017.04.009</a>
Alternative languages
Result language
angličtina
Original language name
Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of 20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney
Original language description
Background: There is vast evidence that the renin-angiotensin system is not the sole determinant of blood pressure (BP) elevation in human renovascular hypertension or the relevant experimental models. This study tested the hypothesis that kidney deficiency of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent omega-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension. Materials and Methods: In 2K1C Goldblatt rats with established hypertension, angiotensin II, angiotensin 1-7, 20-HETE concentrations and gene expression of CYP4A1 enzyme (responsible for 20-HETE formation) of the nonclipped kidney were determined. We examined if 14 days' administration of fenofibrate, a lipid-lowering drug, would increase CYP4A1 gene expression and renal 20-HETE formation, and if increased 20-HETE concentrations in the nonclipped kidney would decrease BP (telemetric measurements). Results: CYP4A1 gene expression, 20-HETE and angiotensin 1-7 concentrations were lower and angiotensin II levels were higher in the nonclipped kidney of 2K1C rats than in sham-operated rats. Fenofibrate increased CYP4A1 gene expression and 20-HETE concentration in the nonclipped kidney and significantly decreased BP in 2K1C rats but did not restore it to normotensive range. The treatment did not change BP in sham-operated rats. Conclusions: Our results suggest that alterations in the RAS and CYP-dependent omega-hydroxylase metabolites of arachidonic acid in the nonclipped kidneys are both important in the pathophysiology of the maintenance phase of 2K1C Goldblatt hypertension. Therefore, fenofibrate treatment effectively attenuated hypertension, probably via stimulation of 20-HETE formation in the nonclipped kidney.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of the Medical Sciences
ISSN
0002-9629
e-ISSN
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Volume of the periodical
353
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
568-579
UT code for WoS article
000403764200014
EID of the result in the Scopus database
2-s2.0-85021859453