MODULATION OF ADPASE AND T-PA RELEASE BY RADIOGRAPHIC CONTRAST-MEDIA IN BOVINE AORTIC ENDOTHELIUM

Vascular endothelial injuries induced by intravascular administration of radiographic contrast agents may be clinically relevant to the deve lopment of thrombosis and platelet activation. In this connection, we investigated the in vitro effects induced by iodamide, iopamidol, and ioxaglate on vascular endothelial ADPase activity and tissue plasminog en activator (t-PA) release in bovine aortic endothelium, in order to extend knowledge required to evaluate endothelial compatibility of rad iographic contrast media. Undiluted and Tris-diluted contrast agent fo rmulations were employed, and mannitol and sucrose hyperosmolar soluti ons were used as comparison. Results demonstrated that the high-osmola r ionic contrast agent iodamide, and to a lesser extent, the low-osmol ar nonionic agent iopamidol, stimulated endothelial ADPase activity of the aortic endothelium; the low-osmolar ionic agent ioxaglate left en dothelial ADPase activity unchanged. Furthermore, the diluted formulat ions of iodamide and iopamidol, as well as high-osmolar mannitol and s ucrose solutions, were devoid of activity in ADPase. This suggests tha t the endothelial ADPase stimulation induced by both radiographic cont rast media was a hyperosmolar-independent pharmacodynamic activity, Io pamidol and ioxaglate reduced endogenous t-PA release from bovine aort ic endothelium only in undiluted formulation, while iodamide showed th is inhibiting action in both diluted and undiluted formulations. No ef fect was observed when using mannitol solutions at different osmolarit y values. Our in vitro findings a ree with published data on the diffe rent thrombotic tendency attributed to the contrast agents used, sugge sting endothelial enzymatic activities (ADPase and t-PA release) as su itable tools for evaluating endothelial vessel wall compatibility with radiographic contrast media. (C) The Italian Pharmacological Society.