EFFECTS OF AGING AND HYPERTENSION ON VASORELAXANT ACTIVITY OF CALCITONIN-GENE-RELATED PEPTIDE - A COMPARISON WITH OTHER VASODILATOR AGENTS

We investigated the influence of aging and hypertension on the vasorel axant effect of calcitonin gene-related peptide (CGRP), examining the responses to stimulation of perivascular vasodilatory nerves and to ad ministration of the peptide in isolated mesenteric vascular bed prepar ations of young (aged 2-3 months) and old (aged 18 months) normotensiv e Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). W e used preparations preconstricted by perfusion with 100 mu M methoxam ine with addition of 5 mu M guanethidine. The stimulation-induced vaso relaxation in the preparations of young SHR animals was significantly lower than that in those of age-matched WKY rats. Moreover, the vasodi later response to stimulation displayed an age-dependent decline in va scular beds of normotensive animals. The degree of the relaxant respon se to CGRP (0.01-1 mu M) did not differ significantly between vascular preparations of normotensive and hypertensive rats; but was significa ntly reduced in preparations of both SHR and WKY rats aged 18 months a s compared with those of young animals. An age-dependent decrement in the vascular reactivity, qualitatively similar to that observed with C GRP, was also detected with two other vasodilators, i.e., the endothel ium-dependent vasodilator acetylcholine (ACh 0.1-100 mu M) and the dir ectly acting nitrovasodilator sodium nitroprusside (SNP, 1-10 mu M). W e conclude that the vascular sensitivity to CGRP, as well as that to o ther vasodilater agents acting by different mechanisms, decreases with age in both normotensive and genetically hypertensive rats.