Nitrite supplementation alleviates cerebrovascular dysfunction in chronically stressed mice, but cognitive decline remains

Abstract This study aimed to determine whether sodium nitrite supplementation prevented chronic stress‐induced cerebrovascular dysfunction and cognitive decline. We hypothesize that nitrite supplementation will prevent the oxidative environment and cerebrovascular dysfunction associated with chronic stress and maintain cognitive health. Eighteen‐week‐old male/female C57BL/6 mice underwent 8 weeks of control conditions or unpredictable chronic mild stress (UCMS) with or without sodium nitrite (50 mg/L) in the drinking water. Excised middle cerebral arteries (MCA) were mounted in a pressurized myobath and exposed to increasing concentrations of acetylcholine (ACh). Nitrite supplementation prevented the UCMS‐induced impaired ACh response in the MCA. We examined xanthine oxidoreductase (XOR) as a potential mechanism by determining XOR protein abundance, activity, and hydrogen peroxide production in the liver and brain. Nitrite supplementation prevented the development of an oxidative environment within the liver, brain and cerebrovasculature. Assessment of working memory revealed that sodium nitrite did not fully prevent the impairment of cognitive function because of chronic stress. These data suggest that nitrite supplementation protects against stressed‐induced cerebrovascular dysfunction by limiting the actions of oxidants, potentially via XOR, while improving NO bioavailability. However, nitrite was not sufficient to prevent cognitive impairment with chronic stress.