title: Iodinated radiographic contrast media inhibit shear stress- and agonist-evoked release of NO by the endothelium.
abstract: 1 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. 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 microM NG-nitro L-arginine methyl ester (L-NAME) and 10 microM 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 approximately 25% and approximately 60%, respectively. Addition of 100 microM NG-nitro L-arginine (L-NOARG) and/or 10 microM 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.
authors.affiliation: Department of Diagnostic Radiology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, U.K.
authors.forename: I R
authors.initials: IR
authors.lastname: Hutcheson
authors.forename: T M
authors.initials: TM
authors.lastname: Griffith
authors.forename: M R
authors.initials: MR
authors.lastname: Pitman
authors.forename: R
authors.initials: R
authors.lastname: Towart
authors.forename: M
authors.initials: M
authors.lastname: Gregersen
authors.forename: H
authors.initials: H
authors.lastname: Refsum
authors.forename: J O
authors.initials: JO
authors.lastname: Karlsson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004285:Dogs; D004431:Ear, External / Q000098:blood supply; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007472:Iohexol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009569:Nitric Oxide / Q000819:agonists* / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship; D014283:Triiodobenzoic Acids / Q000737:chemistry / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014783:Viscosity
chemical_list: D003287:Contrast Media; D004234:Diuretics, Osmotic; D014283:Triiodobenzoic Acids; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D008353:Mannitol; D007472:Iohexol; C038192:iopromide; C044834:iodixanol; D000109:Acetylcholine