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 vasorelaxant effect of calcitonin gene-related peptide (CGRP), examining the responses to stimulation of perivascular vasodilatory nerves and to administration of the peptide in isolated mesenteric vascular bed preparations of young (aged 2-3 months) and old (aged 18 months) normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). We used preparations preconstricted by perfusion with 100 mu M methoxamine with addition of 5 mu M guanethidine. The stimulation-induced vasorelaxation in the preparations of young SHR animals was significantly lower than that in those of age-matched WKY rats. Moreover, the vasodilater response to stimulation displayed an age-dependent decline in vascular beds of normotensive animals. The degree of the relaxant response to CGRP (0.01-1 mu M) did not differ significantly between vascular preparations of normotensive and hypertensive rats; but was significantly reduced in preparations of both SHR and WKY rats aged 18 months as compared with those of young animals. An age-dependent decrement in the vascular reactivity, qualitatively similar to that observed with CGRP, was also detected with two other vasodilators, i.e., the endothelium-dependent vasodilator acetylcholine (ACh 0.1-100 mu M) and the directly acting nitrovasodilator sodium nitroprusside (SNP, 1-10 mu M). We conclude that the vascular sensitivity to CGRP, as well as that to other vasodilater agents acting by different mechanisms, decreases with age in both normotensive and genetically hypertensive rats.