Coagulation Factor Xa Induces Endothelium-Dependent Relaxations in Rat Aorta

Abstract The relaxing effect of coagulation factor Xa on phenylephrine-contracted rat aortic rings was compared with the effect of thrombin and trypsin. All three proteases induced a dose-dependent relaxation in the presence of an intact endothelium. EC50 values were 3±1, 24±9, and 16±1 nmol/L for thrombin, trypsin, and factor Xa, respectively. Whereas thrombin induced rapid relaxations followed by partial recontraction, trypsin and factor Xa induced slower sustained effects. Factor Xa–induced relaxations were not affected by hirudin at high concentrations (1 μmol/L) but were abolished by DX9065A, a specific inhibitor of the catalytic activity of factor Xa. Furthermore, no relaxations to factor Xa could be elicited in the presence of the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (100 μmol/L), whereas relaxations were not altered in the presence of the inactive enantiomer Nω-nitro-d-arginine methyl ester (100 μmol/L). Addition of factor Xa together with thrombin induced relaxations that were l...