Background: Endothelial dysfunction is characterized by decreased vasodilatory capacity of the arterioles mainly due to the reduced release of nitric oxide (NO). Application of NO donors may prevent or even reverse the consequences of endothelial dysfunction, such as diabetic leg ulcers. Objectives: To investigate the vasodilatory capacity and the possible side-effects of topical application of an NO donor-containing hydrogel in diabetic rats. Methods: S-nitrosoglutathione (GSNO) was incorporated in Pluronic® F127 hydrogel and applied on the foot sole skin of healthy and streptozotocin-induced diabetic rats. Blood flow was monitored using a laser-Doppler probe. Nitrotyrosine formation, a possible side-effect of GSNO action, was evaluated by Western blotting of skin protein extracts. Systemic circulatory side-effects were investigated by monitoring blood pressure and heart rate during the application. Results: The hydrogel alone did not induce any changes in microvascular flow, while GSNO-containing hydrogel caused a twofold increase in perfusion. This effect was similar in diabetic and healthy animals. Topical GSNO application did not increase the nitrotyrosine content of skin proteins, nor did it have any effect on blood pressure or heart rate. Conclusions: Dermal application of GSNO may be an effective treatment for promoting the local vasodilation in both healthy and diabetic states, without inducing protein nitration or alterations in blood pressure or heart rate.
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