Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats

Zuzana Honetschlägerová, Alexandra Sporková, Libor Kopkan, Zuzana Husková, Sung H. Hwang, Bruce D. Hammock, John D. Imig, Herbert J. Kramer, Petr Kujal, Zdenka Vernerová, Věra Č Chábová, Vladimír Tesař, Luděk Červenka

Research output: Contribution to journalArticle

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Abstract

Objective: In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. Methods:Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp. Results: I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats. Conclusion: Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.

Original languageEnglish (US)
Pages (from-to)1590-1601
Number of pages12
JournalJournal of Hypertension
Volume29
Issue number8
DOIs
StatePublished - Aug 2011

Fingerprint

Transgenic Rats
Epoxide Hydrolases
Natriuresis
Losartan
Renal Circulation
Hypertension
Kidney
Pressure
Glomerular Filtration Rate
Arterial Pressure
Homeostasis
Malignant Hypertension
Blood Pressure
Xenobiotics
Renin
indole-3-carbinol
Diet
Genes

Keywords

  • AT receptor antagonist
  • cytochrome P-450 metabolites
  • epoxyeicosatrienoic acids
  • malignant hypertension
  • renal autoregulation
  • renin-angiotensin system
  • sodium excretion
  • soluble epoxide hydrolase

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats. / Honetschlägerová, Zuzana; Sporková, Alexandra; Kopkan, Libor; Husková, Zuzana; Hwang, Sung H.; Hammock, Bruce D.; Imig, John D.; Kramer, Herbert J.; Kujal, Petr; Vernerová, Zdenka; Chábová, Věra Č; Tesař, Vladimír; Červenka, Luděk.

In: Journal of Hypertension, Vol. 29, No. 8, 08.2011, p. 1590-1601.

Research output: Contribution to journalArticle

Honetschlägerová, Z, Sporková, A, Kopkan, L, Husková, Z, Hwang, SH, Hammock, BD, Imig, JD, Kramer, HJ, Kujal, P, Vernerová, Z, Chábová, VČ, Tesař, V & Červenka, L 2011, 'Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats', Journal of Hypertension, vol. 29, no. 8, pp. 1590-1601. https://doi.org/10.1097/HJH.0b013e328349062f
Honetschlägerová, Zuzana ; Sporková, Alexandra ; Kopkan, Libor ; Husková, Zuzana ; Hwang, Sung H. ; Hammock, Bruce D. ; Imig, John D. ; Kramer, Herbert J. ; Kujal, Petr ; Vernerová, Zdenka ; Chábová, Věra Č ; Tesař, Vladimír ; Červenka, Luděk. / Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats. In: Journal of Hypertension. 2011 ; Vol. 29, No. 8. pp. 1590-1601.
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abstract = "Objective: In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. Methods:Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp. Results: I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats. Conclusion: Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.",
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T1 - Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats

AU - Honetschlägerová, Zuzana

AU - Sporková, Alexandra

AU - Kopkan, Libor

AU - Husková, Zuzana

AU - Hwang, Sung H.

AU - Hammock, Bruce D.

AU - Imig, John D.

AU - Kramer, Herbert J.

AU - Kujal, Petr

AU - Vernerová, Zdenka

AU - Chábová, Věra Č

AU - Tesař, Vladimír

AU - Červenka, Luděk

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N2 - Objective: In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. Methods:Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp. Results: I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats. Conclusion: Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.

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KW - epoxyeicosatrienoic acids

KW - malignant hypertension

KW - renal autoregulation

KW - renin-angiotensin system

KW - sodium excretion

KW - soluble epoxide hydrolase

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