The role of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in maintenance of hypertension was investigated in the perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone-salt-induced hypertensive rats (DOCA-Salt-HR) and corresponding normotensive control rats (Wistar Kyoto rats, WKY and Wistar rats, NR). In the mesenteric artery with an active tone, the neurogenic vasodilation induced by perivascular nerve stimulation (PNS, 0.5-8 Hz), which was mediated by CGRP nerves, was markedly decreased in adult SHR (15-week-old) when compared with age-matched WKY, whereas the vasodilation in DOCA-Salt-HR was similar in magnitude to that in NR. The vasodilator response to exogenously applied CGRP was greater in SHR than in WKY, whereas no difference was found between DOCA-Salt-HR and NR. The neurogenic release of CGRP-like immunoreactivity (CGRP-LI) induced by PNS of the mesenteric artery was significantly decreased in SHR compared to that of WKY. In addition, immunohistochemical studies showed decreased populations of CGRP-LI fibers in the mesenteric artery of SHR compared to those in WKY. These results suggest that CGRP-containing vasodilator innervation is greatly decreased in SHR with established hypertension. It is also suggested that the decreased vasodilator mechanism by CGRP-containing nerves contributes to the maintenance of hypertension.