Nitrite supplementation preserves aortic endothelial‐dependent vasodilation in chronically stressed mice

Abstract

Chronic stress increases the risk of developing cardiovascular disease potentially via endothelial dysfunction. Decreased bioavailability of the potent vasodilator nitric oxide (NO) describes a hallmark of endothelial dysfunction. Nitrite (NO2-) reduces into active NO, providing an alternative pathway of NO restoration. The effect of nitrite supplementation on aortic endothelial function has yet to be determined in chronically stressed mice. We hypothesized that nitrite supplementation would rescue chronic stress-attributed impairments in aortic endothelial function. Male and female C57Bl/6 mice at 18 weeks-of-age underwent an unpredictable chronic mild stress (UCMS; 5 days/week for 7 hrs/day) paradigm to elicit a chronically stressed phenotype. Control and stressed mice underwent 8 weeks of NO2- supplementation (50mg/L) within their drinking water. At 26 weeks, mice were euthanized, and the thoracic aortas were removed and positioned in a wire myograph chamber. To assess vessel health, the aortas were precontracted with U46619 (7.5x10-9M) and exposed to increasing concentrations of methacholine (MCh; 10-9M to 10-5M) and sodium nitroprusside (SNP; 10-9M to 10-5M). Maximal aorta dilation to MCh was impaired in UCMS mice vs. controls (71±3% vs 87±1%; p<0.05). However, chronic NO2- supplementation prevented the impairment in aortic dilation with UCMS (83±2% vs 71±3%; p<0.05). Maximal aorta dilation to SNP was not affected by UCMS and or NO2- supplementation, with normal aortic smooth muscle dilation. In conclusion, these data suggest an impairment in aortic endothelial function due to chronic stress that is prevented with chronic NO2- supplementation.