EFFECT OF AGE ON THE VASODILATORY ACTION OF ELASTIN PEPTIDES

We have recently shown, on young adult rat aorta rings, that elastin p eptides induce a dose and endothelium-dependent vasodilation mediated by the 67 kDa subunit of the high affinity elastin-laminin receptor an d, at least in part, by EDRF (NO) [1]. Here we have studied the effect s of elastin peptides al circulating concentrations and below, on nora drenaline-contracted rat aortic rings, as a function of age. First, we have observed that, unlike 2-month-old (2M), 4-6-month-old (4M) and 1 2-month-old (12M) rat aorta rings, 30-month-old (30M) rat aorta rings were unable to maintain their contraction in long lasting experiments. Secondly, elastin peptides at physiological circulating concentration s (10(-6)-10(-3) mg/ml) induce a dose-dependent vasodilation on 4M rin gs. By contrast, only higher elastin peptide concentrations (10(-3) mg /ml) were effective on 12M rings, whereas rings from both younger (2M) and older animals (30M) did not respond to elastin peptides. Finally, using lactose and laminin as inhibitors, we have demonstrated that el astin peptide-induced vasodilation on 4M and 12M rings is mediated by the 67 kDa subunit of the elastin-laminin receptor. These experiments suggest that the functional availability of the 67 kDa subunit of the elastin-laminin receptor changes with age. It could be hypothesized th at in young animals (0-2M) the reusable shuttle role recently demonstr ated for the 67 kDa receptor subunit during elastic fiber formation [2 ] leads to a major decrease in its availability for signal transductio n. On the contrary, in adult animals (4-12M), when developmental elast ogenesis is completed, this subunit is essential for extracellular sig nal transduction [3]. Inefficiency of this receptor in old animals (30 M) can be attributed to its uncoupling from its transduction pathway, as previously shown on human cells [4]. Finally, the age-dependent var iations of circulating elastin peptide concentration and elastin-lamin in receptor responsiveness to elastin peptides are two independent par ameters which could influence the vascular tension regulation. (C) 199 7 Elsevier Science Ireland Ltd.