The effects of epinephrine infusion in patients with von Willebrand's disease.

Targeting FVIII expression to endothelial cells regenerates a releasable pool of FVIII and restores hemostasis in a mouse model of hemophilia A

“…It has been shown that epinephrine, which affects vascular motility, increases plasma levels of FVIII:C and VWF:Ag in humans via a cAMP-dependent signaling pathway in responsive cells, which is the same pathway on which DDAVP acts. 38,39 In T2F8 Tg mice, FVIII and VWF release in response to epinephrine increased plasma levels by 68% and 108% respectively, demonstrating that a releasable pool of FVIII in parallel with VWF is reestablished in FVIII null mice when FVIII expression is targeted to endothelial cells. In WT mice, plasma FVIII:C increased approximately 27% after stimulation with epinephrine, which is lower than in T2F8 Tg mice, while VWF:Ag increased to similar levels (121%).…”

Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP

“…Indeed, epinephrine infusion raises plasma vWF levels, and physical activity increases plasma vWF levels by catecholamines acting on β2-adrenergic, AC-coupled receptors (34,35). Most [Ca 2+ ] i -raising agonists are mediators of inflammation and/or thrombosis that also induce cell retraction.…”

The Epac-Rap1 Signaling Pathway Controls cAMP-mediated Exocytosis of Weibel-Palade Bodies in Endothelial Cells

“…Also agonists such as epinephrine and vasopressin that raise intracellular levels of cAMP have been shown to promote the release of WPBs (4,5). The physiological importance of this pathway is illustrated by the rise in VWF levels in patients with von Willebrand disease and mild hemophilia A following administration of the vasopressin analog DDAVP (6) or epinephrine (7). In response to cAMP-mediated stimulation, a subset of WPBs clusters at the microtubule organizing center, which involves retrograde transport of vesicles mediated by the dynein-dynactin complex (8,9).…”