Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney

Xin Zhang, Alfonso Eirin, Zi Lun Li, John A. Crane, James D. Krier, Behzad Ebrahimi, Aditya S. Pawar, Xiang Yang Zhu, Hui Tang, Kyra L. Jordan, Amir Lerman, Stephen C Textor, Lilach O Lerman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.

Original languageEnglish (US)
Pages (from-to)767-775
Number of pages9
JournalKidney International
Volume84
Issue number4
DOIs
StatePublished - Oct 2013

Fingerprint

Valsartan
Angiotensin Receptors
Renal Artery Obstruction
Swine
Glomerular Filtration Rate
Kidney
Angiotensin Receptor Antagonists
Microcirculation
Angiotensin-Converting Enzyme Inhibitors
Therapeutics
Perfusion
Tomography
Sus scrofa
Angiogenesis Inducing Agents
Pathologic Constriction
Oxidative Stress
Hemodynamics
Magnetic Resonance Imaging
Oxygen
Blood Pressure

Keywords

  • angiotensin II type I receptor blockade
  • microvasculature
  • renal artery stenosis

ASJC Scopus subject areas

  • Nephrology

Cite this

Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney. / Zhang, Xin; Eirin, Alfonso; Li, Zi Lun; Crane, John A.; Krier, James D.; Ebrahimi, Behzad; Pawar, Aditya S.; Zhu, Xiang Yang; Tang, Hui; Jordan, Kyra L.; Lerman, Amir; Textor, Stephen C; Lerman, Lilach O.

In: Kidney International, Vol. 84, No. 4, 10.2013, p. 767-775.

Research output: Contribution to journalArticle

Zhang, X, Eirin, A, Li, ZL, Crane, JA, Krier, JD, Ebrahimi, B, Pawar, AS, Zhu, XY, Tang, H, Jordan, KL, Lerman, A, Textor, SC & Lerman, LO 2013, 'Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney', Kidney International, vol. 84, no. 4, pp. 767-775. https://doi.org/10.1038/ki.2013.144
Zhang, Xin ; Eirin, Alfonso ; Li, Zi Lun ; Crane, John A. ; Krier, James D. ; Ebrahimi, Behzad ; Pawar, Aditya S. ; Zhu, Xiang Yang ; Tang, Hui ; Jordan, Kyra L. ; Lerman, Amir ; Textor, Stephen C ; Lerman, Lilach O. / Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney. In: Kidney International. 2013 ; Vol. 84, No. 4. pp. 767-775.
@article{0d529ab505c849c8a92901a9056fef18,
title = "Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney",
abstract = "Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.",
keywords = "angiotensin II type I receptor blockade, microvasculature, renal artery stenosis",
author = "Xin Zhang and Alfonso Eirin and Li, {Zi Lun} and Crane, {John A.} and Krier, {James D.} and Behzad Ebrahimi and Pawar, {Aditya S.} and Zhu, {Xiang Yang} and Hui Tang and Jordan, {Kyra L.} and Amir Lerman and Textor, {Stephen C} and Lerman, {Lilach O}",
year = "2013",
month = "10",
doi = "10.1038/ki.2013.144",
language = "English (US)",
volume = "84",
pages = "767--775",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney

AU - Zhang, Xin

AU - Eirin, Alfonso

AU - Li, Zi Lun

AU - Crane, John A.

AU - Krier, James D.

AU - Ebrahimi, Behzad

AU - Pawar, Aditya S.

AU - Zhu, Xiang Yang

AU - Tang, Hui

AU - Jordan, Kyra L.

AU - Lerman, Amir

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2013/10

Y1 - 2013/10

N2 - Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.

AB - Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.

KW - angiotensin II type I receptor blockade

KW - microvasculature

KW - renal artery stenosis

UR - http://www.scopus.com/inward/record.url?scp=84885294216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885294216&partnerID=8YFLogxK

U2 - 10.1038/ki.2013.144

DO - 10.1038/ki.2013.144

M3 - Article

C2 - 23615504

AN - SCOPUS:84885294216

VL - 84

SP - 767

EP - 775

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -