TY - JOUR
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
N1 - Funding Information:
This study was principally supported by grant No. NT/14011-3 awarded by the Internal Grant Agency of the Ministry of Health (LK). Support was provided by the Ministry of Health of the Czech Republic for the development of research organization 00023001 (institutional support). (AS, LK, LC). Support was provided by the European Commission within the Operational Program Prague–Competitiveness; project “Rozvoj infrastruktury PEM” ( #CZ.2.16/3.1.00/28025 ) (AS, LK, LC). Supported was provided by NIH grant DK38226 (JDI). Supported was provided by Robert A. Welch Foundation ( I-0011 ) and the USPHS NIH ( DK38226 , HL111392 ) (JRF). Support was provided by a Marie Curie Fellowship from the European Commission Program PEOPLE ( IRG 247847 ) (AS).
Publisher Copyright:
© 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
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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U2 - 10.1016/j.amjms.2016.02.030
DO - 10.1016/j.amjms.2016.02.030
M3 - Article
C2 - 27140711
AN - SCOPUS:84970969156
VL - 351
SP - 513
EP - 519
JO - The American journal of the medical sciences
JF - The American journal of the medical sciences
SN - 0002-9629
IS - 5
ER -