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To examine whether the retention of imidazole analogues in the organ rich with elastic connective tissue can be of toxicological significance, the effect of 14C labeled 2-methylimidazole (2MI) as a model compound on the mechanical, biochemical, and morphological properties of the rat aorta, together with its irreversible interaction with the tissue macromolecules, was investigated after chronic treatment during maturation (10 and 100 μmol/kg/day for 28 days, from 4 to 8 weeks of age, subcutaneous injection). 1. Aortic extensibility was significantly decreased in 2MI-dose-dependent manner, whereas tensile strength showed an increasing trend. 2. Aortic elastin content was decreased dose-dependently, while collagen content was increased. 3. The low dose of 2MI scarcely altered histological picture of the aortic wall compared to the control group (isotonic saline dosing), but the high dose caused focal disorganization and fragmentation of the medial elastic laminae. Thickness of the aortic media showed a dose-dependent increasing trend. 4. The level of irreversibly bound 2MI-equivalent in elastin fraction was considerably high as compared with that in non-elastin fraction, and was increased dose-dependently. The aortic microautoradiograph showed that [14C]2MI-derived radioactivity occurred in the media, the region rich with elastic fiber. These findings indicate that 2MI affects maturation of the elastic organ materially, and that the effect can be closely linked with the binding of 2MI to elastin. It is possible that the same holds true for some other imidazole-based compounds that are retained in large quantities in the elastic connective tissue.

Effect of 2-Methylimidazole on the Mechanical, Biochemical, and Morphological Properties of the Rat Aorta by Its Chronic Treatment along Maturation.