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 development 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 plasminogen activator (t-PA) release in bovine aortic endothelium, in order to extend knowledge required to evaluate endothelial compatibility of radiographic contrast media. Undiluted and Tris-diluted contrast agent formulations were employed, and mannitol and sucrose hyperosmolar solutions were used as comparison. Results demonstrated that the high-osmolar ionic contrast agent iodamide, and to a lesser extent, the low-osmolar nonionic agent iopamidol, stimulated endothelial ADPase activity of the aortic endothelium; the low-osmolar ionic agent ioxaglate left endothelial ADPase activity unchanged. Furthermore, the diluted formulations of iodamide and iopamidol, as well as high-osmolar mannitol and sucrose solutions, were devoid of activity in ADPase. This suggests that the endothelial ADPase stimulation induced by both radiographic contrast media was a hyperosmolar-independent pharmacodynamic activity. Iopamidol and ioxaglate reduced endogenous t-PA release from bovine aortic endothelium only in undiluted formulation, while iodamide showed this inhibiting action in both diluted and undiluted formulations. No effect was observed when using mannitol solutions at different osmolarity values. Our in vitro findings agree with published data on the different thrombotic tendency attributed to the contrast agents used, suggesting endothelial enzymatic activities (ADPase and t-PA release) as suitable tools for evaluating endothelial vessel wall compatibility with radiographic contrast media.
Caprino
L
L
Istituto di Farmacologia, University of Rome, La Sapienza, Italy.
Togna
A R
AR
Zappacosta
B
B
Giardina
B
B
Togna
G
G
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism*; D002417:Cattle; D003287:Contrast Media / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007479:Iopamidol / Q000494:pharmacology; D007485:Ioxaglic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D003287:Contrast Media; D010959:Tissue Plasminogen Activator; D001081:Apyrase; D007479:Iopamidol; D007485:Ioxaglic Acid