The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats

Věra Čertíková Chábová, Herbert J. Kramer, Ivana Vaněčková, Monika Thumová, Petra Škaroupková, Vladimír Tesař, John R. Falck, John D. Imig, Luděk Červenka

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Abstract

Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. Methods: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. Results: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. Conclusions: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.

Original languageEnglish (US)
Pages (from-to)335-346
Number of pages12
JournalKidney and Blood Pressure Research
Volume30
Issue number5
DOIs
StatePublished - Sep 2007

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Transgenic Rats
Kidney
Cytochrome P-450 CYP4A
Acids
Sodium
Proteins
Hemodynamics
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Renal Artery
Enzymes
Electrolytes
Sprague Dawley Rats
Western Blotting
High Pressure Liquid Chromatography
Hypertension

Keywords

  • 20-Hydroxyeicosatetraenoic acid
  • Cytochrome P-450
  • Epoxyeicosatrienoic acid
  • Glomerular filtration rate
  • Hypertension
  • Renal plasma flow
  • Renin transgenic rats
  • Renin-angiotensin system
  • Sodium excretion

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Cardiology and Cardiovascular Medicine

Cite this

Čertíková Chábová, V., Kramer, H. J., Vaněčková, I., Thumová, M., Škaroupková, P., Tesař, V., ... Červenka, L. (2007). The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats. Kidney and Blood Pressure Research, 30(5), 335-346. https://doi.org/10.1159/000107710

The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats. / Čertíková Chábová, Věra; Kramer, Herbert J.; Vaněčková, Ivana; Thumová, Monika; Škaroupková, Petra; Tesař, Vladimír; Falck, John R.; Imig, John D.; Červenka, Luděk.

In: Kidney and Blood Pressure Research, Vol. 30, No. 5, 09.2007, p. 335-346.

Research output: Contribution to journalArticle

Čertíková Chábová, V, Kramer, HJ, Vaněčková, I, Thumová, M, Škaroupková, P, Tesař, V, Falck, JR, Imig, JD & Červenka, L 2007, 'The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats', Kidney and Blood Pressure Research, vol. 30, no. 5, pp. 335-346. https://doi.org/10.1159/000107710
Čertíková Chábová, Věra ; Kramer, Herbert J. ; Vaněčková, Ivana ; Thumová, Monika ; Škaroupková, Petra ; Tesař, Vladimír ; Falck, John R. ; Imig, John D. ; Červenka, Luděk. / The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats. In: Kidney and Blood Pressure Research. 2007 ; Vol. 30, No. 5. pp. 335-346.
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abstract = "Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. Methods: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. Results: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. Conclusions: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.",
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T1 - The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats

AU - Čertíková Chábová, Věra

AU - Kramer, Herbert J.

AU - Vaněčková, Ivana

AU - Thumová, Monika

AU - Škaroupková, Petra

AU - Tesař, Vladimír

AU - Falck, John R.

AU - Imig, John D.

AU - Červenka, Luděk

PY - 2007/9

Y1 - 2007/9

N2 - Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. Methods: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. Results: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. Conclusions: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.

AB - Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated. Methods: Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay. Results: TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics. Conclusions: Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.

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KW - Cytochrome P-450

KW - Epoxyeicosatrienoic acid

KW - Glomerular filtration rate

KW - Hypertension

KW - Renal plasma flow

KW - Renin transgenic rats

KW - Renin-angiotensin system

KW - Sodium excretion

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