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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11 Scopus citations

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 1 2007

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

  • Nephrology
  • Cardiology and Cardiovascular Medicine

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    Čertíková Chábová, V., Kramer, H. J., Vaněčková, I., Thumová, M., Škaroupková, P., Tesař, V., Falck, J. R., Imig, J. D., & 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