Undergraduate Honors Theses

Thesis Defended

Spring 2019

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Integrative Physiology

First Advisor

Douglas Seals

Second Advisor

Mark Opp

Third Advisor

Jessica Gorski

Abstract

Age is the primary risk factor for cardiovascular disease (CVD). Adverse changes to arteries, including the development of vascular endothelial dysfunction, mediate the age-related increase in risk of CVD. Endothelial dysfunction is a consequence of insufficient nitric oxide (NO) bioavailability, secondary to increased oxidative stress. Inorganic nitrite supplementation is a novel strategy to improve NO bioavailability. Accordingly, a recent pilot study in our laboratory, showed that 12 weeks of sodium nitrite supplementation improved endothelial function measured as brachial artery flowmediated dilation (FMD) in healthy middle-aged and older (MA/O) adults. Here, we sought to confirm our pilot study findings by conducting a larger randomized, placebocontrolled, double-blind, parallel group study with 12 weeks of sodium nitrite (80mg/day) vs. placebo in MA/O adults (n=49, 68±1 yr) with impaired endothelial function (baseline brachial artery FMD <6%). Sodium nitrite increased plasma nitrite levels acutely (10- fold, p<0.05 vs. placebo) and chronically (p<0.05) and was safe and well tolerated. Vascular endothelial function, as measured by brachial artery FMD, was increased by 28% as compared to baseline (3.9±1.2 to 5.0±1.8%, p<0.05), but unchanged with placebo (3.8±1.4 to 4.0±1.5%, p>0.05). Endothelial cell expression of nitrotyrosine, a marker of oxidative stress, was decreased by 54% after sodium nitrite supplementation (p=0.034), but unchanged with placebo; endothelial cell markers of antioxidant status (manganese superoxide dismutase), inflammation (nuclear factor kappa B), and endothelial NO synthase were unaffected, as were participant characteristics and circulating factors (all p>0.05). These data suggest sodium nitrite supplementation improves endothelial function in healthy MA/O adults, possibly by reducing oxidative stress.

Available for download on Wednesday, March 17, 2021

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