Calcitonin gene-related peptide-mediated depressor effect and inhibiting vascular hypertrophy of rutaecarpine in renovascular hypertensive rats

Calcitonin gene-related peptide-mediated depressor effect and inhibiting vascular hypertrophy of rutaecarpine in renovascular hypertensive rats
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降钙素基因相关肽介导的降压作用及吴茱萸碱对肾血管性高血压大鼠血管肥大的抑制作用

DOI:
10.1097/fjc.0b013e3181579e7e
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发表时间:
2007-12-01
影响因子:
3
通讯作者:
Li, Yuan-Jian
Li, Yuan-Jian
中科院分区:
医学4区
文献类型:
--
作者:
Qin, Xu-Ping;Zeng, Si-Yu;Li, Yuan-Jian

文献摘要

被引文献

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降钙素基因相关肽(CGRP)是辣椒素敏感感觉神经中的主要神经递质,具有强大的血管扩张剂和抑制血管平滑肌细胞增殖的作用。既往研究表明,吴茱萸次碱(RUT)的降压作用与苯酚诱导的高血压大鼠CGRP合成和释放通过激活香草素受体1亚型(VR1)有关。本研究在2肾1夹(2K1C)高血压大鼠模型上检测了RUT的降压作用和抑制血管肥厚的作用是否由内源性CGRP介导。用尾套法测定清醒状态下的收缩压。分离肠系膜动脉,观察其形态变化。测定大鼠血浆CGRP浓度及背根神经节(DRG)CGRP基因表达。慢性给予RUT(分别为10、20、40 mg/kg/d)4周,可引起高血压大鼠降压作用,显著缩小管腔直径,减少肠系膜动脉中膜厚度,同时增加血浆CGRP浓度和DRG中CGRP mRNA的表达。结论:长期给予RUT可降低2K1C高血压大鼠血压,减轻系膜动脉肥厚,其作用机制可能与促进CGRP合成和释放有关。
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 mesentenic artery hypertrophy in the 2K1C hypertensive rats, and the effects of Rut may be related to stimulation of CGRP synthesis and release.