Age-Related Changes in Calcitonin Gene-Related Peptide (CGRP)-Mediated Neurogenic Vasodilation of the Mesenteric Resistance Vessel in SHR

Age-related changes in CGRP-containing vasodilator nerve activity in hypertension were studied in perfused mesenteric vascular beds isolated from SHR and normotensive rats (WKY). Perivascular nerve stimulation (PNS; 0.5-8 Hz) of both SHR and WKY preparations with active tone produced a frequency-dependent vasodilator response, which was abolished by 100 nM tetrodotoxin, 500 nM capsaicin or cold storage denervation. This response in SHR greatly decreased with age, whereas the response in WKY slightly decreased with age. The neurogenic vasodilation in 15- and 30-week-old SHR but not 8-week-old SHR was significantly smaller than that in age-matched WKY. Vasodilator responses to exogenous CGRP (0.1-30 nM) in SHR increased with age, whereas an age-related decrease in the vasodilation was found in WKY. Immunohistochemical studies showed an age-related decrease in CGRP-containing fibers in SHR. These results suggest that CGRP-containing vasodilator innervation is greatly decreased when SHR develop and maintain hypertension.