Enhancing Parasympathetic Activity to Improve Endothelial Dysfunction, Vascular Oxidative Stress in African Americans

FMD,NADPH activation in PBMC

Specific Aim 1: To test the hypothesis that prolonged (3-month) treatment with galantamine
 inhibits NADPH IsoLG-protein adducts formation and improves markers of endothelial cell (EC)
 dysfunction in AAs.
 
 Aim 1a: The investigators will determine if galantamine inhibits NADPH IsoLG-protein adducts
 formation, superoxide production, and immune cell activation compared to placebo.
 
 For this purpose, the investigators will study peripheral blood mononuclear cell (PBMC), a
 critical source of systemic oxidative stress, collected from study participants.
 
 Aim 1b: The investigators will determine if galantamine reduces intracellular Iso-LGs,
 ICAM-1, and 3-nitrotyrosine, a marker of vascular oxidative stress, in ECs harvested from
 study participants.
 
 Specific Aim 2: To determine if prolonged (3-month) treatment with galantamine improves
 endothelial dysfunction as measured by vascular reactivity in AAs. The investigators will
 measure vascular reactivity in response to ischemia in two vascular beds: (a) in conduit
 arteries (brachial artery) using brachial artery diameter flow-mediated dilation (FMD), and
 (b) in the microvasculature (MBV) using contrast-enhanced ultrasonography in skeletal muscle.
 
 This proposal will study a novel mechanism that could alter the oxidative and immunogenic
 responses that contributes to endothelial dysfunction in AAs and will offer a potential
 pathway for the development of more effective therapies aimed at decreasing the progression
 of endothelial dysfunction to cardiovascular disease in this population.