Angiographic contrast media relax isolated rabbit aorta through an endothelium-independent mechanism that may not depend on the presence of the iodine atom

Abstract

Systemically administered iodinated angiographic contrast media evoke vasodilatation through mechanisms that are at present poorly understood. In the current investigation we have evaluated the role of the vascular endothelium in responses to an iso-osmolar formation of the non-ionic dimer iodixanol and a hyperosmolar formulation of the non-ionic monomer iopromide. Isolated rabbit aortic ring preparations with endothelium intact or removed by gentle abrasion were mounted in organ baths containing oxygenated Holman's solution, and cumulative concentration-response curves for relaxation to the contrast media were constructed after pre-constriction by phenylephrine (300 nM) in the presence of indomethacin to inhibit prostaglandin synthesis. Endothelial denudation did not influence the ability of either iodixanol or iopromide to relax the aortic ring preparations. Iopromide was significantly more potent than iodixanol when expressed in terms of iodine concentration (mg I ml-1), but both agents were equipotent when expressed in terms of molarity (mM). We conclude that relaxation of isolated rabbit aortic rings to iodixanol and iopromide under conditions where there is no fluid flow is endothelium-independent, and therefore not mediated by release of the potent endogeneous nitrovasodilator endothelium-derived relaxing factor (EDRF). Furthermore, their relaxant activity under the in vitro experimental conditions employed is attributable to a direct action on vascular smooth muscle by factors in addition to osmolality, and may depend on features that are not specifically associated with the presence of the iodine atom.

Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta

“…The present data also show that iodixanol causes a smaller degree of relaxation than iohexol at equivalent iodine concentrations consistent with in vivo studies demonstrating that iodixanol (320 mg I ml-') is a less potent vasodilator than either iohexol (320 mg I ml-1) or iopromide (300 mg I ml-) in femoral arteries of dogs (Almen, 1987) and man (Pugh et al, 1993). However, when relaxation of the isolated rings was plotted as a function of molarity, the concentration-relaxation curves for both agents could be superimposed, analogous to the findings of Pugh et al (1995b). By comparison, the concentration-relaxation curve for mannitol was shifted downwards and to the right, and maximal relaxation was only 25-30% of that produced by equivalent molar concentrations of the contrast agents.…”

“…Indeed, recent studies have demonstrated that peripheral vasodilatation and patient discomfort during aortofemoral angiography is significantly greater with nonionic monomers than the new iso-osmolar dimeric contrast agent iodixanol, at concentrations providing equivalent radiographic contrast (Pugh et al, 1993;Verow et al, 1995). Nevertheless, formulations of iodixanol that are iso-osmotic with blood still cause significant vasodilatation both in animal models and clinically (Almen 1987;Pugh et al, 1992;1995b). The exact mechanisms underlying IRCM-induced vasodilatation consequently remain incompletely understood.…”

“…We have also compared their relaxant activity with that of mannitol at similar molar concentrations. In previous experiments from this laboratory we employed 'ready-to-use' formulations of IRCM (Pugh et al, 1995b), whereas in the present study pure compounds were dissolved directly into physiological buffer to eliminate secondary effects due to alterations in the net ionic composition of the incubation medium.…”

Effects of iodinated contrast media on common carotid and brachial artery blood flow and wall shear stress

“…Nevertheless, CM can still influence vascular tone and either vasodilatation or vasoconstriction have been described. The intrinsic properties of these agents, osmolality and viscosity, have been suggested as mediators of the observed modifications [1,[18][19][20][21]. It has been hypothesized that intra-arterial injection of CM might induce vasodilatation after the activation of the endothelium KATP channel, which is sensitive to shear stress.…”

The iodinated radiographic contrast medium iohexol mimics the vasodilator effect seen with small increases in extracellular K+ in the isolated rabbit central ear artery

“…Guided by Torsten Almén's ideas (1,2), the osmolalities of IRCM have been considerably reduced, which has largely eliminated the intravascular injection-related pain. However, IRCM with osmolalities close or identical to that of blood also exhibit vasodilator properties, although to a lesser extent than their high-osmolality counterparts (17,20,(22)(23)(24). This suggests that other properties in addition to hyperosmolality may also contribute to this effect.…”