Effects of Aging and Hypertension on Vasorelaxant Activity of Calcitonin Gene-related Peptide: A Comparison with Other Vasodilator Agents

Summary: We investigated the influence of aging and hypertension on the vasorelaxant effect of calcitonin generelated 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 μM methoxamine with addition of 5 μM 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 vasodilator 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 μM) 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 μM) and the directly acting nitrovasodilator sodium nitroprusside (SNP, 1-10 μM). We conclude that the vascular sensitivity to CGRP, as well as that to other vasodilator agents acting by different mechanisms, decreases with age in both normotensive and genetically hypertensive rats.