Abstract P154: Central Acetylcholinesterase Inhibitor, Galantamine, Prevents Lipid-Induced Oxidative Stress in African Americans

Abstract

African American women (AAW) have one of the highest prevalence of hypertension in the US. Obese AAW have decreased parasympathetic (PNS) activity compared to white women (WW). Continuous lipid infusion that causes cardiovascular autonomic imbalance (decrease in PNS and increase in sympathetic activity) induces a greater increase in oxidative stress in African Americans than in whites. Considering that PNS protects against oxidation and that central acetylcholinesterase inhibitors have been shown to suppress oxidative stress in animal models; we tested the hypothesis that the central acetylcholinesterase inhibitor, galantamine attenuates oxidation in response to lipid infusion in obese AAW compared to WW. We randomized 14 healthy obese AAW (39.5±10.7 yo, BMI 38.8±3.4) and 10 WW (35.9±8.3 yo, BMI 36.3±2.1). All subjects underwent 4-h infusions of Intralipids and heparin. On separate days subjects received either 16 mg galantamine or placebo in a crossover fashion. Lipid-induced oxidative stress and inflammation were assessed with plasma F2-isoprostanes and cytokines at baseline, 2 and 4-h post-intralipid infusion. In AAW, 16 mg of galantamine significantly suppressed the increase in lipid-induced oxidative stress (-3±12 vs. 10±18 pg/mL with placebo, P=0.014), figure . No effect was noted in WW. Galantamine tended to increase IL10 levels (17.3±20.7 vs. 4.8±7.58 pg/mL, P=0.06). We did not observe any effect on blood pressure or heart rate. Conclusion: Increased parasympathetic tone with central acetylcholinesterase inhibitor, galantamine, suppressed lipid-induced oxidative stress in obese African American women.