Cortical microvascular remodeling in the stenotic kidney: role of increased oxidative stress.

Abstract

OBJECTIVE:

Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress.

METHODS AND RESULTS:

Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 microm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1alpha, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1alpha mRNA expression. In contrast, expression of HIF-1alpha, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention.

CONCLUSIONS:

Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.

• Authors: Xiang-Yang Zhu, Alejandro R Chade, Martin Rodriguez-Porcel, Michael D Bentley, Erik L Ritman, Amir Lerman, Lilach O Lerman
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 10 Pg. 1854-9 (Oct 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 15308558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Animals
• Female
• Kidney Cortex (blood supply, pathology)
• Neovascularization, Pathologic (pathology)
• Oxidation-Reduction
• Oxidative Stress (physiology)
• Renal Artery Obstruction (blood, pathology)
• Swine