Calcitonin gene-related Peptide-mediated depressor effect and inhibiting vascular hypertrophy of rutaecarpine in renovascular hypertensive rats.
Calcitonin gene-related peptide (CGRP), the predominant neurotransmitter in capsaicin-sensitive sensory nerves, is a potent vasodilator and inhibits proliferation of vascular smooth muscle cells. Previous investigations have demonstrated that the hypotensive effect of rutaecarpine (Rut) is associated to stimulation of CGRP synthesis and release via activation of the vanilloid receptor subtype 1 (VR1) in the phenol-induced hypertensive rat. This study tested whether the depressor effect and inhibiting vascular hypertrophy of Rut is mediated by endogenous CGRP in 2-kidney, 1-clip (2K1C) hypertensive rats. Systolic blood pressure (SBP) was measured by tail-cuff method in conscious. Mesenteric arteries were isolated for examination of morphological changes. The concentration of CGRP in the plasma and the expression of CGRP mRNA in dorsal root ganglia (DRG) were measured. Chronic administration of Rut (10, 20, or 40 mg/kg/day, respectively) for 4 weeks caused a depressor effect and significantly regressed the lumen diameter and decreased the medium thickness of mesenteric arteries in hypertensive rats concomitantly with an increase in the plasma concentration of CGRP and the expression of CGRP mRNA in DRG. In conclusion, chronic administration of Rut can reduce blood pressure and relieve mesenteric artery hypertrophy in the 2K1C hypertensive rats, and the effects of Rut may be related to stimulation of CGRP synthesis and release.
Qin
Xu-Ping
XP
Department of Pharmacology, University of South China, Hengyang, China.
Zeng
Si-Yu
SY
Li
Dai
D
Chen
Qing-Quan
QQ
Luo
Dan
D
Zhang
Zhe
Z
Hu
Gao-Yun
GY
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006984:Hypertrophy; D007022:Hypotension / Q000139:chemically induced; D026121:Indole Alkaloids / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D052999:Quinazolinones
D047228:Angiotensin II Type 1 Receptor Blockers; D015740:Calcitonin Gene-Related Peptide; D026121:Indole Alkaloids; D019808:Losartan; D011799:Quinazolines; D012333:RNA, Messenger; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones