Dietary Nitrate Supplementation Improves Revascularization in Chronic Ischemia
Background—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 and other nitrogen oxides, enhances ischemia-induced remodeling of the vascular network is not known.
Methods and Results—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 S-nitrosothiols, nitrite, and skeletal tissue cyclic guanosine monophosphate (cGMP) levels were assessed. EGFP (enhanced green fluorescence protein) transgenic mice were used for bone marrow transplantation. Dietary nitrate increased plasma S-nitrosothiols and nitrite, enhanced revascularization, increased mobilization of CD34+/Flk-1+ and migration of bone-marrow derived CD31+/CD45- cells to the site of ischemia, and attenuated 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.
- Received April 17, 2012.
- Accepted August 10, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited