In present study, we examined the effects of NG-nitro-L-arginine (LNNA), an inhibitor of nitric oxide synthase (NOS), and/or methylene blue (MB), a blocker of guanylate cyclase on the vasodilator response of isolated rat arteries including aorta and mesenteric artery to calcitonin gene-related peptide (CGRP) by in vitro vasoconstriction experiment, and the effect of LNNA on the depressor action of CGRP by in vivo hemodynamic experiment. Furthermore, the effect of CGRP on NOS activity and cyclic guanylate monophosphate (cGMP) content were also examined by NOS activity assay and radioimmunoassay (RIA), respectively. The results showed that LNNA and/or MB significantly decreased, but not abolished, the vasodilator response of isolated rat aorta and mesenteric artery to CGRP. The depressor effect of CGRP on LNNA-induced hypertensive rats (LHR) was obviously weaker than that on spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive rats (NWR). In addition, CGRP (0.5 nmol/kg) increased the NOS activity of rat aorta tissue by 1.3 times (P < 0.05) and resulted in an increase of cGMP content of aorta (1.27 times, P < 0.05) and myocardium (1.38 times, P < 0.05). The results suggested that NO is involved in the action of CGRP.