Date of Graduation
School of Medicine
Chronic stress increases the risk of developing cardiovascular disease potentially via increases in elastic artery stiffness and endothelial dysfunction. Decreased bioavailability of the potent vasodilator nitric oxide (NO) describes a hallmark of endothelial dysfunction. Nitrite 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.
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 nitrite 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). Aortic intrinsic mechanical stiffness and carotid pulse wave velocity were further measured. IHC staining of abdominal aorta was conducted for total collagen and medial elastin content.
Maximal thoracic aorta percent dilation to MCh was impaired in mice that underwent UCMS when compared to controls (71±11% vs 87±6%; p
In conclusion, these data suggest an impairment in aortic endothelial function due to chronic stress that is alleviated upon supplementation with nitrite.
Coblentz, Tyler, "Nitrite Supplementation Restores Aortic Health in Chronically Stressed Mice" (2021). Graduate Theses, Dissertations, and Problem Reports. 8265.
Available for download on Thursday, July 28, 2022