Access Type

Open Access Dissertation

Date of Award


Degree Type


Degree Name




First Advisor

John M. Flack


Salt sensitivity is associated with a rise in blood pressure (BP) occurring during sodium loading and/or a fall in BP during sodium restriction that exceeds random fluctuations in BP. Salt sensitivity is more common in African American than Caucasian hypertensives and is also present, in normotensive African Americans. The mechanism or mechanisms resulting in salt-sensitive hypertension are multiple and include both activation of the renin angiotensin system via increases in angiotensin II and reductions in the endogenous vasodilator, nitric oxide (NO). An important means of NO downregulation is through asymmetric dimethylarginine (ADMA), an endogenous NO inhibitor, which is largely metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). The activity of DDAH is impaired by oxidative stress, thereby permitting ADMA to accumulate thus resulting in further inhibition of NO. Increases in oxidative stress, reduction in DDAH activity, and augmented action of ADMA on depressing NO production represents a plausible mechanism in human salt sensitivity. The study investigates and characterizes the above mechanism through which salt-induced depression of NO synthesis occurs in normotensive African Americans. The study population was a cohort of mostly young (mean age 45 years, SD = 6.0), female (87%), African Americans who were normotensive, and overweight. The DDAH level and NO metabolites came down after sodium exposure (6.17% and 11.53%, respectively), while the BP rose (SBP: +2.8 mm Hg; DBP +0.8 mm Hg) and the augmentation index (a measure of arterial stiffness) increased by almost 12% after sodium exposure, though not statistically significant. The difference in sodium:creatinine ratio was directly proportional to the change in BP (SBP: p = 0.01; DBP p = 0.13), which likely mediated the BP effect. Additionally, NO metabolites and DDAH levels were positively correlated to each other (r = 0.90; p = 0.0001), and changes in both DDAH and NO levels were negatively correlated to changes in augmentation index (DDAH: r = -0.61; p = 0.04; NO: r = -0.59; p = 0.05). As expected, the DDAH and NO levels increased while the augmentation index decreased reflecting a reduction in arterial stiffness. Overall, in a cohort of young, overweight, African American normotensive women, sodium exposure was directly proportional to the difference in BP and there was a reduction in DDAH level and NO metabolites, with significant indirect correlations between DDAH, NO, and augmentation index. Despite lack of significance in the differences of DDAH, ADMA, and NO between the treatment groups, the combined group results trended in the direction of the central hypothesis that increased dietary sodium intake downregulates DDAH and depresses NO production, resulting in a rise in BP and vascular stiffness. This initial study is the first demonstrating the trend that increased sodium intake was associated with a reduction in DDAH activity, and a depression in NO metabolites in healthy, normotensive African Americans.