Preservation of pressure-induced cutaneous vasodilation by limiting oxidative stress in short-term diabetic mice

Objective: Pressure-induced vasodilation (PIV) allows skin blood flow to increase in response to locally applied pressure and may be protective against pressure ulcers. We previously showed that PIV was absent in 1-week diabetic mice exhibiting no neuropathy. Our aim was to determine whether the diabetes-induced PIV alteration could be prevented. Methods and results: Diabetic mice received no treatment or a daily treatment with either sorbinil, alagebrium or alpha-lipoic acid (LPA) for I week. Laser Doppler flowmetry was used to evaluate PIV as well as endothelium-dependent vasodilation following iontophoretic delivery of acetylcholine (ACh). The effect of each treatment on oxidative stress was examined by plasma 8-isoprostane assay. LPA was the sole treatment to prevent both PIV and ACh vasodilation alterations, with a significant reduction of oxidative stress in diabetic mice. Both PIV and ACh-vasodilation were abolished in LPA-treated diabetic mice following injection of N-omega-nitro-L-arginine (p < 0.05). In contrast, alagebrium, and sorbinil prevented neither diabetes-induced PIV abolition nor endothelial alteration. Conclusions: LPA treatment significantly reduced the oxidative stress and was able to preserve endothelial nitric oxide availability in the cutaneous microcirculation and then to preserve the PIV response in diabetic mice. LPA treatment could play a key role in limiting the risk of pressure-induced cutaneous ulcer during diabetes. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.