Dietary nitrate supplementation improves revascularization in chronic ischemia

Area of Science:

• Physiology
• Vascular Biology
• Nutrition Science

Background:

• Revascularization is a critical repair process for ischemic tissues, with nitric oxide playing a key role.
• The potential of dietary nitrate, converted to nitric oxide via oral bacteria, to aid this process remains unexplored.

Purpose of the Study:

• To investigate whether dietary nitrate supplementation enhances ischemia-induced vascular remodeling.
• To determine the role of oral commensal bacteria in mediating the effects of dietary nitrate on revascularization.

Main Methods:

• Mice received dietary nitrate or a control for 14 days, followed by hind-limb surgery to induce ischemia.
• Assessed blood flow, capillary density, cell mobilization (CD34+/Flk-1+), cell migration (bone marrow-derived CD31+/CD45-), and apoptosis.
• Investigated the role of oral bacteria using an antiseptic mouthwash to eradicate nitrate-reducing bacteria.

Main Results:

• Dietary nitrate increased plasma nitrite and S-nitrosothiols, indicating effective conversion.
• Enhanced revascularization, increased mobilization and migration of key stem cells to ischemic sites.
• Reduced apoptosis of regenerative myoblasts and improved blood flow recovery.
• Abolition of these regenerative effects by eradicating oral nitrate-reducing bacteria.

Conclusions:

• Long-term dietary nitrate supplementation shows potential as a nutrition-based strategy to improve ischemia-induced revascularization.
• The conversion of nitrate to nitric oxide by oral bacteria is essential for mediating these beneficial effects.