1 We have used rings of rabbit thoracic aorta to investigate the vasorelaxant properties of two different classes of non-ionic iodinated radiographic contrast media (IRCM) and the mechanisms, underlying their mode of action. lohexol (a triiodinated monomer) was compared with iodixanol (a hexaiodinated dimer).2 lohexol and iodixanol both relaxed phenylephrine (0.3 gM) constricted rabbit aorta in a concentration-dependent manner that did not depend on the presence of an intact endothelium. When expressed as a function of iodine concentration, iodixanol caused significantly less relaxation than iohexol. However, the extent of relaxation was similar for both IRCM when expressed on a molar basis. Furthermore, increasing the molarity of the buffer to comparable levels with mannitol evoked only a small (-15%) relaxation of phenylephrine-induced tone.3 Ouabain (10 gM) significantly inhibited both iohexol-and iodixanol-induced relaxations by -30%.5-(N-Ethyl-N-isopropyl)-amiloride (EIPA, 100 nM) significantly inhibited iohexol-induced relaxation to the same extent as ouabain, but did not alter the vasorelaxant effect of iodixanol. Co-incubation with ouabain and EIPA had an additive effect in the case of iohexol, increasing inhibition of relaxation to -60%, whereas inhibition of iodixanol-induced relaxation by the combination of ouabain plus EIPA did not differ from that of ouabain alone. 4 Replacing NaCl with N-methyl-D-glucamine (NMDG) to lower extracellular [Na+] and thereby inhibit Na+ -Ca2" exchange, attenuated the relaxation evoked by iohexol or by iodixanol (by -25%) in each case. 5 We conclude that iohexol-and iodixanol-induced vasorelaxation in rabbit aorta is mediated through a direct action on vascular smooth muscle that is not simply a consequence of altered osmolality. It involves modulation of the Na+-K+ ATPase and, in the case of iohexol, Na+-H+ exchange. Both agents also appear to modulate Na+ -Ca2+ exchange, through direct and/or indirect mechanisms. This is the first study to show specific pharmacological differences between monomeric and dimeric contrast media in vascular smooth muscle.
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 triiodinated monomers iopromide and iohexol were compared with the hexa-iodinated dimer iodixanol. 2 The vasodilator e ects of iohexol (300 mg ml 71 ) and iodixanol (320 mg ml 71 ) were assessed in cascade bioassay. Increasing concentrations of iohexol or iodixanol caused concentration-dependent relaxations of the detector tissue which were insensitive to 100 mM N G -nitro L-arginine methyl ester (L-NAME) and 10 mM 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 endotheliumdenuded rings were una ected. 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 71 ) and iopromide (300 mg ml 71 ) administered as close arterial bolus attained a plateau with maximal dilatations of *25% and *60%, respectively. Addition of 100 mM N G -nitro L-arginine (L-NOARG) and/or 10 mM indomethacin to the perfusate had no e ect on the responses to either agent. 5 We conclude that IRCM exert direct e ects 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.