The differential effect of contrast agents on endothelial cell and smooth muscle cell growth in vitro

Purpose: This study was designed to evaluate the effects of ionic and nonionic contrast agents on endothelial cell (EC) and smooth muscle cell (SMC) proliferation, and to determine the role of osmolality as the etiology of these effects. Methods: Cultured bovine aorta EC and SMC were exposed to ionic (iothalamate meglumine) or nonionic (ioversol or iopamidol) contrast, or varying osmolar solutions of mannitol, for periods of 1, 3, 5, 10, or 20 minutes. Cells were then incubated in growth media at 37 degrees C and proliferation and structure were assessed 1, 3, 5, and 7 days later. Results: Both EC and SMC showed decreased proliferation after brief exposure to both ionic and nonionic contrast. Proliferation was markedly decreased at 24 hours after exposure, and began to recover by day 3 after exposure. EC showed a significant decrease up to 7 days after exposure to ionic contrast (p < 0.03), whereas SMC showed a significant decrease up to 7 days after exposure to nonionic contrast (p < 0.001). The decrease in proliferation was directly dependent on the length of exposure to the contrast and the concentration of the contrast. EC proliferation decreased in proportion to increasing osmolality of the test solution (p < 0.05). SMC proliferation did not show a decrease proportional to osmolality. No change was observed in cell viability as assessed by LDH activity studies. After contrast exposure, bare areas with no cells present were noted in the previously confluent EC and SMC culture wells. Cell structure was altered immediately after exposure to contrast, with normal structure recovered by 24 hours after exposure. Conclusion: This study demonstrates that brief exposure to contrast agents injures EC and SMC, altering their structure and decreasing proliferation for up to 7 days in vitro. This response is both dose and time dependent. EC are more severely affected by ionic contrast, and SMC are more severely affected by nonionic contrast. EC injury appears to be mediated by the osmolar effect of the contrast, but the effects of contrast on SMC seem to be due to a different mechanism.