Antioxidant vitamins induce angiogenesis in the normal pig kidney

Abstract

The effects of chronic supplementation with antioxidant vitamins on angiogenesis are controversial. The aim of the present study was to evaluate in kidneys of normal pigs the effect of chronic supplementation with vitamins E and C, at doses that are effective in reducing oxidative stress and attenuating angiogenesis under pathological conditions. Domestic pigs were randomized to receive a 12-wk normal diet without (n = 6) or with antioxidant vitamins supplementation (1g/day vitamin C, 100 IU.kg(-1).day(-1) vitamin E; n = 6). Electron beam computed tomography (CT) was used to evaluate renal cortical vascular function in vivo, and micro-CT was to assess the spatial density and average diameter of cortical microvessels (diameter <500 microm) ex vivo. Oxidative stress and expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha were evaluated in renal tissue. The effects of increasing concentrations of the same vitamins on redox status and angiogenesis were also evaluated in human umbilical vascular endothelial cells (HUVEC). Compared with normal pigs, the density of cortical transmural microvessels was significantly greater in vitamin-supplemented pigs (149.0 +/- 11.7 vs. 333.8 +/- 48.1 vessel/cm(2), P < 0.05), whereas the cortical perfusion response to ACh was impaired. This was accompanied by a significant increase in tissue oxidative stress and levels of VEGF and HIF-1alpha. A low dose of antioxidant decreased, whereas a high dose increased, HUVEC oxidative stress and angiogenesis, which was partly mediated by hydrogen peroxide. Antioxidant vitamin supplementation can increase tissue oxidative redox and microvascular proliferation in the normal kidney, probably due to a biphasic effect that depends on basal redox balance.