DDAVP Infusion Does Not Affect Plasma Levels of Endothelin-1 in Four Normal Subjects

It is well known that desmopressin acetate (l-deamino-8-Darginine vasopressin, DDAVP) increases plasma factor VIII, von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA)» çonςentrations with no important side effects when given intravenously to healthy subjects and to patients with hemophilia and von Willebrand disease (1), DDAVP also induces systemic release of urokinase-type plasminogen activator in normal sub­ jects (2). However, many aspects of the mechanism of DDAVP action are not clarified and it is not known whether DDAVP is able to provoke the release of other substances present in the endothelial cells. Recently, it has been shown that DDAVP infusion does not induce the release of fibronectin which is also produced by endothelial cells (3). Similarly, no changes were observed as far as concerns thrombomodulin, the endothelial cell surface membrane protein which binds thrombin with high affinity and acts as a cofactor for thrombin-catalyzed activation of anticoagulant protein C (4). Accordingly, it has been suggested that the elevated levels of circulating thrombomodulin reported in patients with collagen disease, diabetes mellitus and disseminated intravascular coagulation do not represent, unlike vWF and t-PA, a marker of endothelial cell stimulation, but only reflect endothe­ lial injury. Also plasma concentrations of endothelin-1, the novel endothelium-derived peptide with a potent and sustained con­ strictive effect on a variety of blood vessels, seem to remain unchanged after DDAVP infusion (5). However, in that study the dosage of DDAVP was too low in comparison of those generally used and the effect on vWF and t-PA not compared. Thus, we decided to examine the effect in normal subjects of a conventional dose of DDAVP on the endothelin-1 plasma levels simultane­ ously with those of vWF and t-PA. Four healthy subjects (2 women and 2 men; age range 25-30 years) participated in the study giving their informed consent. Blood samples were collected in basal conditions, after a 30 min infusion of saline and after various intervals (15, 30, 60 and 120 min) from the beginning of an infusion of DDAVP (Minirin, Ferring, Malmö, Sweden) at the dose of 0.3 μg/kg over 30 min. Plasma levels of t-PA antigen and vWF antigen were measured by commercial ELISA methods (American Diagnostica, New York, NY and Boehringer, Mannheim, Germany, respectively). Endothelin-1 was assessed in plasma after elution from prepared Bond Elut C18 solid-phase catridges (Analytichem International) with a radioimmunoassay (Amersham Interna­ tional). Statistical analysis was performed by the Student's ŕ-test for paired data. Our results indicate that the infusion of DDAVP (0.3 μg/kg in 30 min) induces a significant increase of vWF after 30 min from the beginning of the infusion and after 60 and 120 min. t-PA levels were also significantly increased after 30 and 60 min. By contrast, endothelin-1 levels remained unchanged (see Table 1), thus indicating that the elevated concentrations of endothelin-1 observed in some pathological conditions [cardiogenic shock (6), Raynaud's phenomenon (7), etc.] do not represent a marker of endothelial cell stimulation.