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

Vasopressin and its analogue 1-deamino-8-D-arginine vasopressin (DDAVP) are known to raise plasma von Willebrand factor (vWF) levels. DDAVP is used as a hemostatic agent for the treatment of von Willebrand's disease. However, its cellular mechanisms of action have not been elucidated DDAVP, a specif ic agonist for the vasopressin V2 receptor (V2R), exerts its antidiuretic e ffect via a rise in cAMP in kidney collecting ducts. We tested the hypothes is that DDAVP induces vWF secretion by binding to V2R and activating cAMP-m ediated signaling in endothelial cells. vWF secretion from human umbilical vein endothelial cells (HUVECs) can be mediated by cAMP, but DDAVP is ineff ective, presumably due to the absence of V2R. We report that DDAVP stimulat es vWF secretion in a cAMP-dependent manner in HUVECs after transfection of the V2R In addition, vasopressin and DDAVP induce vWF secretion in human l ung microvascular endothelial cells (HMVEC-L). These cells (but not HUVECs) express endogenous V2R, as shown by RT-PCR. Vasopressin-induced,vWF secret ion is mimicked by DDAVP and inhibited by the selective V2R antagonist SR12 1463B. It is mediated by cAMP, since it is inhibited by the protein kinase A inhibitor Rp-8CPT-cAMPS. These results indicate that vasopressin induces cAMP-mediated vWF secretion by a direct effect on endothelial cells. They a lso demonstrate functional expression of V2R in endothelial cells, and prov ide a cellular mechanism for the hemostatic effects of DDAVP.