Iodinated radiographic contrast media inhibit shear stress- and agonist-evoked release of NO by the endothelium

1 We have used isolated arterial preparations from the rabbit and dog to investigate whether nonionic iodinated radiographic contrast media (IRCM) modulate nitric oxide (NO) release. The tri-iodinated monomers iopromide and iohexol were compared with the hexa-iodinated dimer iodixanol. 2 The vasodilator effects of iohexol (300 mg ml(-1)) and iodixanol (320 mg ml(-1)) were assessed in cascade bioassay. Increasing concentrations of iohexol or iodixanol caused concentration-dependent relaxations of the detector tissue which were insensitive to 100 mu M N-G-nitro L-arginine methyl eater (L-NAME) and 10 mu M indomethacin, whereas viscosity-associated relaxations induced by the 'inert' agent dextran (MW 80,000; 1-4%) were attenuated by inhibition of NO synthesis. 3 Relaxations of endothelium-intact rings to acetylcholine (ACh) were attenuated by preincubation with iohexol or iodixanol. whereas relaxations to sodium nitroprusside (SNP) in endothelium-denuded rings were unaffected. Inhibitory activity did not correlate with either molarity or iodine concentration. Mannitol caused inhibition of both ACh- and SNP-induced responses. 4 In isolated perfused arteries the depressor responses to iodixanol (320 mg ml(-1)) and iopromide (300 mg ml(-1)) administered as close arterial bolus attained a plateau with maximal dilatations of similar to 25% and similar to 60%, respectively. Addition of 100 mu M N-G-nitro L-arginine (L-NOARG) and/or 10 mu M indomethacin to the perfusate had no effect on the responses to either agent. 5 We conclude that IRCM exert direct effects on the endothelium that inhibit NO production rather than its action on vascular smooth muscle. Shear stress-induced stimulation of NO production by IRCM is unlikely to contribute to their vasodilator activity in vivo when administered during angiography despite high intrinsic viscosity.