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Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of 20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney.

Abstract 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 ω-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension.
PMID
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Authors

Mayor MeshTerms
Keywords

1-clip Goldblatt hypertension

20-hydroxyeicosatetraenoic acid

Cytochrome P450 metabolites

Renin-angiotensin system

Two-kidney

Journal Title the american journal of the medical sciences
Publication Year Start




PMID- 28641720
OWN - NLM
STAT- MEDLINE
DA  - 20170623
DCOM- 20170628
LR  - 20170628
IS  - 1538-2990 (Electronic)
IS  - 0002-9629 (Linking)
VI  - 353
IP  - 6
DP  - 2017 Jun
TI  - Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of
      20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney.
PG  - 568-579
LID - S0002-9629(17)30215-X [pii]
LID - 10.1016/j.amjms.2017.04.009 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Southern Society for Clinical Investigation. Published by
      Elsevier Inc. All rights reserved.
FAU - Sporkova, Alexandra
AU  - Sporkova A
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic.
FAU - Certikova Chabova, Vera
AU  - Certikova Chabova V
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic; Department of Nephrology, 1st Faculty of
      Medicine, Charles University, Prague, Czech Republic.
FAU - Dolezelova, Sarka
AU  - Dolezelova S
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic.
FAU - Jichova, Sarka
AU  - Jichova S
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic.
FAU - Kopkan, Libor
AU  - Kopkan L
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic.
FAU - Vanourkova, Zdenka
AU  - Vanourkova Z
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic.
FAU - Kompanowska-Jezierska, Elzbieta
AU  - Kompanowska-Jezierska E
AD  - Department of Renal and Body Fluid Physiology, Mossakowski Medical Research
      Centre, Polish Academy of Sciences, Warsaw, Poland.
FAU - Sadowski, Janusz
AU  - Sadowski J
AD  - Department of Renal and Body Fluid Physiology, Mossakowski Medical Research
      Centre, Polish Academy of Sciences, Warsaw, Poland.
FAU - Maxova, Hana
AU  - Maxova H
AD  - Department of Pathophysiology, 2nd Faculty of Medicine, Charles University,
      Prague, Czech Republic.
FAU - Cervenka, Ludek
AU  - Cervenka L
AD  - Center for Experimental Medicine, Institute for Clinical and Experimental
      Medicine, Prague, Czech Republic; Department of Pathophysiology, 2nd Faculty of
      Medicine, Charles University, Prague, Czech Republic. Electronic address:
      [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170412
PL  - United States
TA  - Am J Med Sci
JT  - The American journal of the medical sciences
JID - 0370506
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Hypolipidemic Agents)
RN  - 79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
RN  - U202363UOS (Fenofibrate)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Fenofibrate/*pharmacology/*therapeutic use
MH  - Hydroxyeicosatetraenoic Acids/*deficiency
MH  - Hypertension, Renovascular/*drug therapy/physiopathology
MH  - Hypolipidemic Agents/pharmacology/therapeutic use
MH  - Kidney/*drug effects/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - 1-clip Goldblatt hypertension
OT  - 20-hydroxyeicosatetraenoic acid
OT  - Cytochrome P450 metabolites
OT  - Renin-angiotensin system
OT  - Two-kidney
EDAT- 2017/06/24 06:00
MHDA- 2017/06/29 06:00
CRDT- 2017/06/24 06:00
PHST- 2016/11/16 [received]
PHST- 2017/04/07 [revised]
PHST- 2017/04/10 [accepted]
AID - S0002-9629(17)30215-X [pii]
AID - 10.1016/j.amjms.2017.04.009 [doi]
PST - ppublish
SO  - Am J Med Sci. 2017 Jun;353(6):568-579. doi: 10.1016/j.amjms.2017.04.009. Epub
      2017 Apr 12.