Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats

Agnieszka Walkowska, Petra Škaroupková, Zuzana Husková, Zdenka Vaňourková, Věra Čertíková Chábová, Vladimír Tesař, Herbert J. Kramer, John R. Falck, John D. Imig, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. Methods: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, ω-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. Results: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. Conclusion: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.

Original languageEnglish (US)
Pages (from-to)582-593
Number of pages12
JournalJournal of Hypertension
Volume28
Issue number3
DOIs
StatePublished - Mar 2010

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Surgical Instruments
Arachidonic Acid
Cytochrome P-450 Enzyme System
Kidney
Hemodynamics
Sodium
Renal Artery
Hypertension
Epoxide Hydrolases
Renovascular Hypertension
Acids
Mixed Function Oxygenases
Electrolytes
Sprague Dawley Rats
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Proteins

Keywords

  • 20-hydroxyeicosatetraenoic acid
  • Cytochrome P-450 metabolites
  • Epoxyeicosatrienoic acids
  • Renal function
  • Renin-angiotensin system
  • Two-kidney one-clip Goldblatt hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats. / Walkowska, Agnieszka; Škaroupková, Petra; Husková, Zuzana; Vaňourková, Zdenka; Chábová, Věra Čertíková; Tesař, Vladimír; Kramer, Herbert J.; Falck, John R.; Imig, John D.; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Červenka, Luděk.

In: Journal of Hypertension, Vol. 28, No. 3, 03.2010, p. 582-593.

Research output: Contribution to journalArticle

Walkowska, A, Škaroupková, P, Husková, Z, Vaňourková, Z, Chábová, VČ, Tesař, V, Kramer, HJ, Falck, JR, Imig, JD, Kompanowska-Jezierska, E, Sadowski, J & Červenka, L 2010, 'Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats', Journal of Hypertension, vol. 28, no. 3, pp. 582-593. https://doi.org/10.1097/HJH.0b013e328334dfd4
Walkowska, Agnieszka ; Škaroupková, Petra ; Husková, Zuzana ; Vaňourková, Zdenka ; Chábová, Věra Čertíková ; Tesař, Vladimír ; Kramer, Herbert J. ; Falck, John R. ; Imig, John D. ; Kompanowska-Jezierska, Elzbieta ; Sadowski, Janusz ; Červenka, Luděk. / Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats. In: Journal of Hypertension. 2010 ; Vol. 28, No. 3. pp. 582-593.
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abstract = "Objective: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. Methods: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, ω-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. Results: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. Conclusion: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.",
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T1 - Intrarenal cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip Goldblatt hypertensive rats

AU - Walkowska, Agnieszka

AU - Škaroupková, Petra

AU - Husková, Zuzana

AU - Vaňourková, Zdenka

AU - Chábová, Věra Čertíková

AU - Tesař, Vladimír

AU - Kramer, Herbert J.

AU - Falck, John R.

AU - Imig, John D.

AU - Kompanowska-Jezierska, Elzbieta

AU - Sadowski, Janusz

AU - Červenka, Luděk

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N2 - Objective: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. Methods: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, ω-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. Results: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. Conclusion: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.

AB - Objective: The contribution of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) as cytochrome P-450 metabolites of arachidonic acid in the regulation of the nonclipped kidney function in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats was investigated during the phases of initial and stable hypertension, that is, 7 or 27 days after clipping, respectively. Methods: Male Hannover Sprague-Dawley rats had the right renal artery clipped or underwent sham operation. Urinary excretion of EETs, their inactive metabolites dihydroxyeicosatrienoic acids and of 20-HETE was measured. Intrarenal cytochrome P-450 protein expression and the activities of epoxygenase, ω-hydroxylase and soluble epoxide hydrolase were also determined. The responses of renal hemodynamics and electrolyte excretion of the nonclipped kidney to left renal artery infusions of inhibitors of EETs or 20-HETE formation (MS-PPOH and DDMS, respectively) were measured. Results: In 2K1C rats, urinary excretion of EETs was significantly lower and that of 20-HETE was higher than that in sham-operated animals only on day 27 after clipping. Intrarenal inhibition of EETs significantly decreased renal hemodynamics and sodium excretion in sham-operated but not in 2K1C rats. Intrarenal inhibition of 20-HETE decreased sodium excretion in sham-operated rats but elicited increases in renal hemodynamics and sodium excretion in 2K1C rats. Conclusion: Our results indicate that the nonclipped kidney of Goldblatt 2K1C rats in the phase of sustained hypertension exhibits decreased intrarenal EETs and elevated 20-HETE levels as compared with the kidney of sham-operated animals. This suggests that altered production and action of cytochrome P-450-derived metabolites during this stable phase contributes to the mechanism of Goldblatt 2K1C hypertension.

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KW - Renin-angiotensin system

KW - Two-kidney one-clip Goldblatt hypertension

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