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

Autor: Hutcheson IR; Department of Diagnostic Radiology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, U.K., Griffith TM, Pitman MR, Towart R, Gregersen M, Refsum H, Karlsson JO
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 1999 Sep; Vol. 128 (2), pp. 451-7.
DOI: 10.1038/sj.bjp.0702781
Abstrakt: 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.
Databáze: MEDLINE
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