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Desmopressin (DDAVP) induces NO production in human endothelial cells via V2 receptor‐ and cAMP‐mediated signaling
Author(s) -
Kaufmann J. E.,
Iezzi M.,
Vischer U. M.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00197.x
Subject(s) - enos , endocrinology , medicine , vasodilation , vasopressin , forskolin , agonist , chemistry , wortmannin , receptor , signal transduction , biology , microbiology and biotechnology , pi3k/akt/mtor pathway , nitric oxide synthase , nitric oxide
Summary. The hemostatic agent desmopressin (DDAVP) also has strong vasodilatory effects. DDAVP is a selective agonist for the vasopressin V2 receptor (V2R), which is coupled to cAMP‐dependent signaling. DDAVP‐induced vasodilation may be due to endothelial NO synthase (eNOS) activation. This hypothesis implies cAMP‐mediated eNOS activation. It also implies wide extrarenal, endothelial V2R expression. We show that in human umbilical vein endothelial cells (HUVECs) the cAMP‐raising agents forskolin and epinephrine increase NO production, as measured by a l ‐NMMA‐inhibitable rise in cellular cGMP content. They also increase eNOS enzymatic activity, in a partly calcium‐independent manner. cAMP‐mediated eNOS activation is associated with phosphorylation of residue Ser1177, in a phosphatidyl inositol 3‐kinase (PI3K)‐independent manner. HUVECs do not express V2R. However, after heterologous V2R expression, DDAVP induces cAMP‐dependent eNOS activation via Ser1177 phosphorylation. We have previously found V2R expression in cultured lung endothelial cells. By real time quantitative RT‐PCR, we now find a wide V2R distribution notably in heart, lung and skeletal muscle. These results indicate that DDAVP and other cAMP‐raising agents can activate eNOS via PI3K‐independent Ser1177 phosphorylation in human endothelial cells. This mechanism most likely accounts for DDAVP‐induced vasodilation.