Interlobular arteries from 2-kidney, 1-clip goldblatt hypertensive rats' exhibit-im paired vasodilator response to epoxyeicosatr ienoic acids

Alexandra Sporková, Rami N. Redd, J R Falck, John D. Imig, Libor Kopkan, Janusz Sadowski, Ludek Cervenka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. Materials and Methods: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-etherEET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4% versus 80.4 ± 6%, and for native EETs they were 41.7 ± 6.6% versus 62.8 ± 4.4% (P ≤ 0.05 for each difference). Conclusions: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension.

Original languageEnglish (US)
Pages (from-to)513-519
Number of pages7
JournalAmerican Journal of the Medical Sciences
Volume351
Issue number5
DOIs
StatePublished - 2016

Fingerprint

Vasodilator Agents
Surgical Instruments
Arteries
Kidney
Acids
Blood Vessels
Renovascular Hypertension
Renal Artery
Blood Pressure
Renal Hypertension
Phenylephrine
Angiotensin II
Biological Availability
Animal Models
Hemodynamics
Maintenance

Keywords

  • 1-Clip Goldblatt hypertension
  • 2-Kidney
  • Epoxyeicosatrienoic acids
  • Renovascular hypertension
  • Vasodilatory responses

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Interlobular arteries from 2-kidney, 1-clip goldblatt hypertensive rats' exhibit-im paired vasodilator response to epoxyeicosatr ienoic acids. / Sporková, Alexandra; Redd, Rami N.; Falck, J R; Imig, John D.; Kopkan, Libor; Sadowski, Janusz; Cervenka, Ludek.

In: American Journal of the Medical Sciences, Vol. 351, No. 5, 2016, p. 513-519.

Research output: Contribution to journalArticle

Sporková, Alexandra ; Redd, Rami N. ; Falck, J R ; Imig, John D. ; Kopkan, Libor ; Sadowski, Janusz ; Cervenka, Ludek. / Interlobular arteries from 2-kidney, 1-clip goldblatt hypertensive rats' exhibit-im paired vasodilator response to epoxyeicosatr ienoic acids. In: American Journal of the Medical Sciences. 2016 ; Vol. 351, No. 5. pp. 513-519.
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title = "Interlobular arteries from 2-kidney, 1-clip goldblatt hypertensive rats' exhibit-im paired vasodilator response to epoxyeicosatr ienoic acids",
abstract = "Background: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. Materials and Methods: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-etherEET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8{\%} versus 49.8 ± 7.2{\%} in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4{\%} versus 80.4 ± 6{\%}, and for native EETs they were 41.7 ± 6.6{\%} versus 62.8 ± 4.4{\%} (P ≤ 0.05 for each difference). Conclusions: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension.",
keywords = "1-Clip Goldblatt hypertension, 2-Kidney, Epoxyeicosatrienoic acids, Renovascular hypertension, Vasodilatory responses",
author = "Alexandra Sporkov{\'a} and Redd, {Rami N.} and Falck, {J R} and Imig, {John D.} and Libor Kopkan and Janusz Sadowski and Ludek Cervenka",
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T1 - Interlobular arteries from 2-kidney, 1-clip goldblatt hypertensive rats' exhibit-im paired vasodilator response to epoxyeicosatr ienoic acids

AU - Sporková, Alexandra

AU - Redd, Rami N.

AU - Falck, J R

AU - Imig, John D.

AU - Kopkan, Libor

AU - Sadowski, Janusz

AU - Cervenka, Ludek

PY - 2016

Y1 - 2016

N2 - Background: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. Materials and Methods: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-etherEET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4% versus 80.4 ± 6%, and for native EETs they were 41.7 ± 6.6% versus 62.8 ± 4.4% (P ≤ 0.05 for each difference). Conclusions: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension.

AB - Background: Small renal arteries have a significant role in the regulation of renal hemodynamics and blood pressure (BP). To study potential changes in the regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the 2-kidney, 1-clip Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) that are believed to be involved in the regulation of renal vascular function and BP. A total of 2 newly synthesized EET analogues were also examined. Materials and Methods: Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine, pressurized and the effects of a 14,15-EET analogue, native 14,15-EET and 11,12-etherEET-8ZE, an analogue of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results: In the arteries from nonclipped kidneys isolated in the maintenance phase of Goldblatt hypertension, the maximal vasodilatory response to 14,15-EET analogue was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4 ± 6.4% versus 80.4 ± 6%, and for native EETs they were 41.7 ± 6.6% versus 62.8 ± 4.4% (P ≤ 0.05 for each difference). Conclusions: We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal angiotensin II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2-kidney, 1-clip Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension.

KW - 1-Clip Goldblatt hypertension

KW - 2-Kidney

KW - Epoxyeicosatrienoic acids

KW - Renovascular hypertension

KW - Vasodilatory responses

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