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 mm Hg for Cap2+2K1C and 2K1C groups, respectively, p<0.01; mean arterial pressure was 185.2+/-6.6 and 150.5+/-4.1 mm 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.
Deng
Pan-Yue
PY
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 88, Xiang-Ya Road, Changsha, Hunan 410078, China.
Ye
Feng
F
Zhu
Hui-Qing
HQ
Cai
Wei-Jun
WJ
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D012333:RNA, Messenger; D015740:Calcitonin Gene-Related Peptide