Previous investigations have indicated that calcitonin gene-related peptide (CGRP) plays an important role in the regulation of cardiovascular function, and that the development of hypertension may be related to the reduction of sensory vasodilator nerve actions. In the present study, we examined the effect of perindopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on the plasma level and synthesis of CGRP in 2 kidneys, 1-clip hypertensive rats (2K1C, Goldblatt). In the hypertension group, systolic blood pressure and mean artery pressure were raised, and the level of CGRP in plasma was slightly raised compared with control groups. Chronic treatment with losartan or perindopril significantly increased the plasma concentration of CGRP and the expression of CGRP mRNA in dorsal root ganglia in the 2K1C, Goldblatt hypertensive rats. These results suggest that the 2K1C, Goldblatt hypertensive model has a compensatory increase of sensory nerve actions, and that the depressor effects of perindopril or losartan may be related to stimulation of the synthesis and release of CGRP in the 2K1C, Goldblatt hypertensive rats.