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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2861-2867.)
© 1997 American Heart Association, Inc.

Articles

Evidence Against an Effect of Endothelin-1 on Blood Coagulation, Fibrinolysis, and Endothelial Cell Integrity in Healthy Men

Stylianos Kapiotis; Bernd Jilma; Tivadar Szalay; Eva Dirnberger; Oswald Wagner; Hans-Georg Eichler; ; Wolfgang Speiser

From the Department of Clinical Pharmacology (S.K., B.J., T.S., E.D., H.-G.E.) and the Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.K., O.W., W.S.), University of Vienna, Vienna, Austria.

Correspondence to Wolfgang Speiser, MD, c/o Department of Clinical Pharmacology, General Hospital Vienna, Währinger Gürtel 18-20, A-1090 Wien, Austria. E-mail stylianos.kapiotis{at}univie.ac.at

Abstract On the basis of an array of preclinical experimental results, it has been widely assumed that endothelin-1 (ET-1) may affect blood coagulation, fibrinolysis, and endothelial cell function, thereby playing a pathophysiological role in various cardiovascular diseases in humans. However, confirmation of this assumption is still lacking. ET-1 or placebo was administered intravenously to 12 healthy volunteers in a prospective, randomized, double-blind, crossover trial. Pathophysiologically relevant concentrations of ET-1 (an approximate threefold increase of normal blood levels) causing hemodynamic effects were reached by continuous intravenous infusion for 6 hours. Components of the coagulation (thrombin-antithrombin complexes, prothrombin fragment F₁₊₂, activated factor VII, and factor VII antigen) and fibrinolytic (fibrin split product D-dimer, plasmin–plasmin inhibitor complex, tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1) systems and markers of endothelial cell perturbation/dysfunction (von Willebrand factor and thrombomodulin) were measured before the start of infusion and after 2, 6, 12, and 24 hours. Comparing changes in the plasma concentrations of these parameters during and after infusion of ET-1 and placebo, we found no specific effects of ET-1. In contrast to previous reports from preclinical experiments, ET-1 does not appear to affect coagulation or fibrinolysis, nor does this peptide induce relevant endothelial cell perturbations in humans.

Key Words: endothelin • coagulation • fibrinolysis • von Willebrand factor • endothelium

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