Ir. Hutcheson et al., Iodinated radiographic contrast media inhibit shear stress- and agonist-evoked release of NO by the endothelium, BR J PHARM, 128(2), 1999, pp. 451-457
1 We have used isolated arterial preparations from the rabbit and dog to in
vestigate whether nonionic iodinated radiographic contrast media (IRCM) mod
ulate nitric oxide (NO) release. The tri-iodinated monomers iopromide and i
ohexol 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 ioh
exol or iodixanol caused concentration-dependent relaxations of the detecto
r tissue which were insensitive to 100 mu M N-G-nitro L-arginine methyl eat
er (L-NAME) and 10 mu M indomethacin, whereas viscosity-associated relaxati
ons 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 atten
uated by preincubation with iohexol or iodixanol. whereas relaxations to so
dium nitroprusside (SNP) in endothelium-denuded rings were unaffected. Inhi
bitory activity did not correlate with either molarity or iodine concentrat
ion. Mannitol caused inhibition of both ACh- and SNP-induced responses.
4 In isolated perfused arteries the depressor responses to iodixanol (320 m
g ml(-1)) and iopromide (300 mg ml(-1)) administered as close arterial bolu
s 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 inhibi
t NO production rather than its action on vascular smooth muscle. Shear str
ess-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.