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 microM methoxamine with addition of 5 microM 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 microM) 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 microM) and the directly acting nitrovasodilator sodium nitroprusside (SNP, 1-10 microM). 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.
Amerini
S
S
Department of Pharmacology, University of Florence, Italy.
Mantelli
L
L
Filippi
S
S
Ledda
F
F
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004558:Electric Stimulation; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D066298:In Vitro Techniques; D008729:Methoxamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013152:Splanchnic Circulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D008729:Methoxamine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine