Radiocontrast media induced endothelin-1 mRNA expression and peptide release in porcine aortic endothelial cells.

Endothelin-1 (ET-1) is a powerful vasoconstrictor, primarily secreted by vascular endothelial cells. It may be an important mediator for radiocontrast-induced renal vasoconstriction, which may cause acute renal failure in susceptible subjects. This study measured the release of ET-1 by cultured porcine endothelial cells under incubation with various radiocontrast agents. Compared with the control group, the conventional ionic radiocontrast, diatrizoate, induced a dose- and time-dependent increase in ET-1 release. The lowest concentration of diatrizoate required to induce an increase in ET-1 secretion was 1 mM, less than the estimated serum level (about 5.2 mM) in clinical radiographic practice, suggesting that a direct release of ET-1 from endothelial cells may take place in clinical image studies. The stimulation effect of the following contrast agents on endothelial ET-1 release was compared: diatrizoate (ionic monomer), ioxaglate (ionic dimer), iohexol (nonionic monomer), iotrolan (nonionic dimer). Higher levels of ET-1 release were stimulated by ionic agents compared to the nonionic agents, but no difference in the degree of stimulation was observed between the monomeric and dimeric forms. All agents significantly increased ET-1 release compared with the control group. ET-1 production stimulated by radiocontrast agents was independent of hyperosmolality and was primarily seen as an increase in ET-1 mRNA. The increase in ET-1 release was actinomycin D-sensitive, and ET-1 mRNA abundance was greatly enhanced by cycloheximide. The augmented ET-1 mRNA expression to radiocontrast treatment was not secondary to the enhanced message stability. The data suggest that the contrast media-induced increments in ET-1 release are transcription-dependent and that both ionic and nonionic radiocontrast agents have a renal vasoconstrictive effect that is mediated by ET-1 and may potentially be nephrotoxic in susceptible subjects. Nonionic agents may be less toxic.