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.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.forename: Zi-Lun
authors.initials: ZL
authors.lastname: Li
authors.forename: John A
authors.initials: JA
authors.lastname: Crane
authors.forename: James D
authors.initials: JD
authors.lastname: Krier
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: Aditya S
authors.initials: AS
authors.lastname: Pawar
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003251:Constriction, Pathologic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012078:Renal Artery Obstruction / Q000150:complications* / Q000503:physiopathology; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine