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

We have used isolated arterial preparations from the rabbit and dog to investigate whether non‐ionic 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. 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 μ M N G ‐nitro L ‐arginine methyl ester ( L ‐NAME) and 10 μ M indomethacin, whereas viscosity‐associated relaxations induced by the ‘inert’ agent dextran (MW 80,000; 1–4%) were attenuated by inhibition of NO synthesis. 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. 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 ∼25% and ∼60%, respectively. Addition of 100 μ M N G ‐nitro L ‐arginine ( L ‐NOARG) and/or 10 μ M indomethacin to the perfusate had no effect on the responses to either agent. 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.British Journal of Pharmacology (1999) 128 , 451–457; doi: 10.1038/sj.bjp.0702781