An increase in the synthesis and release of calcitonin gene-related peptide in two-kidney, one-clip hypertensive rats

Previous investigations have indicated that capsaicin-sensitive sensory nerves play an important role in modulation of the peripheral resistance of the circulation system. In the present study, we examined the role of capsaicin-sensitive sensory nerves in two-kidney, one-clip (2K1C) renovascular hypertension rats. Systolic blood pressure (BP) was monitored by the tail-cuff method throughout the experiment. Concentrations of calcitonin gene-related peptide (CGRP) in the plasma, the level of CGRP mRNA in dorsal root ganglia (DRG) and the density of CGRP immunoreactive (CGRP-ir) fibers in mesenteric artery were measured. Blood pressure was significantly elevated at day 10 postoperation (BP was 143 +/- 10 and 114 +/- 7 mm Hg for 2K1C and Sham groups, respectively, p<0.05). Treatment with capsaicin, which selectively depletes neurotransmitters in sensory nerves, enhanced hypertensive responses to clipping (BP was 168 +/- 7 and 143 +/- 10 mm Hg at day 10 postoperation for Cap1 +2K1C and 2K1C groups, respectively, p<0.05), and BP in the rats treated with a second injection of capsaicin was greater than that in the rats treated with a single injection of capsaicin (At day 30 postoperation, BP was 199 +/- 7 and 166 +/- 9 turn Hg for Cap2+2K1C and 2K1C groups, respectively, p<0.01; mean arterial pressure was 185.2 +/- 6.6 and 150.5 +/- 4.1 nun Hg for Cap2 +2K1C and 2K1C groups, respectively, p < 0.01). The expression of alpha-CGRP mRNA in DRG (122.87 +/- 3.67 arbitrary units, p<0.05), the level of CGRP in the plasma (75.40 +/- 4.99 pg/ml, p<0.01) and the density of CGRP-ir fibers in mesenteric artery (525.67 +/- 31.42 intersections, p < 0.05) were significantly increased in 2K1C rats. Treatment with capsaicin, a single injection or a second injection, prevented the increased in the expression of CGRP mRNA in DRG. However, the decreased level of CGRP was only observed in the rats treated with a second capsaicin. These results suggest that in 2K1C hypertensive rats, the activity of capsaicin-sensitive sensory nerves is increased, which is playing a compensatory depressor role to partially counteract the increase in blood pressure, and that the cardiovascular actions of CGRP is mediated by the alpha-CGRP isoform. (C) 2003 Elsevier Science B.V. All rights reserved.