Abstract
Purpose Revascularization is an adaptive repair mechanism that restores blood flow to undersupplied ischemic tissue. Nitric oxide (NO ) plays an important role in this process. Whether dietary nitrate, serially reduced to nitrite by commensal bacteria in the oral cavity and subsequently to NO , enhances ischemia-induced remodeling of the vascular network is not known. The present study was to assess the effects of dietary nitrate supplementation on ischemia-induced revascularization. Methods Mice were treated with either nitrate (1 g/L sodium nitrate in drinking water) or sodium chloride (control) for 14 days. At day 7, unilateral hindlimb surgery with excision of the left femoral artery was conducted. Blood flow was determined by laser doppler. Capillary density, myoblast apoptosis, mobilization of CD34+/Flk-1+, migration of bone-marrow derived CD31+/CD45−, plasma nitrite, nitrate and nitrosothiols as well as skeletal tissue cGMP levels were assessed. EGFP (enhanced green fluorescence protein) transgenic mice were used for bone marrow transplantation. Results Dietary nitrate supplementation leads to increased circulating nitrosothiol levels. Moreover nitrate supplementation enhances revascularization, increases mobilization of CD34+/Flk-1+ and migration of bone-marrow derived CD31+/CD45− cells to the site of ischemia, and attenuates apoptosis of potentially regenerative myoblasts in chronically ischemic tissue. The regenerative effects of nitrate treatment were abolished by eradicating nitrate-reducing bacteria in the oral cavity through an antiseptic mouthwash. Conclusions Chronic dietary nitrate supplementation may represent a novel nutrition-based strategy to enhance ischemia-induced revascularization. Disclosure Nothing to disclose.
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