Effects of Epinephrine on Atherothrombotic Responses and In Vivo Endothelial Function in Healthy Humans

In this study we have tested the hypothesis that levels of epinephrine simulating those occurring during hypoglycemia of 70, 60, or 50 mg/dl will result in pro-coagulant and pro-atherothrombotic responses and endothelial dysfunction. 32 healthy humans (16M/16F) participated in 4 separate, single blind, randomized, 1-day studies: Placebo (Protoco1 1) and epinephrine infusions of 0.015, 0.03 and 0.06µg/kg/min (Protocols 2-4) respectively. Studies consisted of 2-hour hyperinsulinemic (133±7µU/ml) euglycemic clamps of 92±1mg/dl. 2D Doppler imaging determined flow mediated dilation (FMD) of the brachial artery. Increases of IL-6, P-selectin, E-selectin, ICAM-1, and VCAM-1 were higher and reductions in FMD and ET-1 greater during all epinephrine infusions compared to Placebo (p Epinephrine activated pro-coagulant, inflammatory and pro-atherothrombotic mechanisms while impairing endogenous and exogenous nitric oxide mediated endothelial function. In conclusion, during hyperinsulinemic euglycemia, epinephrine levels simulating those occurring during hypo of only 70mg/dl produced significant inflammatory effects. Increasing doses of epinephrine resulted in greater inflammatory responses and in-vivo endothelial dysfunction (p Disclosure M. Mikeladze: None. M. Hedrington: None. S. Dumbadze: None. V.J. Briscoe: None. D. Tate: None. E. Thayer: None. S. Davis: None.