Letter Regarding Article, Receptor activity-modifying protein-1 augments cerebrovascular responses to calcitonin gene-related peptide and inhibits angiotensin II-induced vascular dysfunction.
Letter Regarding Article, Receptor activity-modifying protein-1 augments cerebrovascular responses to calcitonin gene-related peptide and inhibits angiotensin II-induced vascular dysfunction.
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关于文章的信件，受体活性修饰蛋白-1 增强脑血管对降钙素基因相关肽的反应，并抑制血管紧张素 II 诱导的血管功能障碍。
DOI：
10.1161/strokeaha.110.604272
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发表时间：
2011
期刊：
影响因子：
8.3
通讯作者：
et al.
中科院分区：
文献类型：
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作者：
Kazushi Tsuda;et al.
我们怀着极大的兴趣阅读了Chrissobolis博士及其同事1最近发表的一篇文章，该文章涉及降钙素基因相关肽（CGRP）受体的受体活性修饰蛋白1（RAMP 1）过表达的转基因小鼠的脑血管反应。他们的研究结果表明，与对照组相比，在人RAMP 1转基因小鼠中，颈动脉和基底动脉以及体内脑小动脉中对CGRP的反应选择性增强。此外，作者提出，RAMP1表达后，血管紧张素II诱导的氧化应激和内皮功能障碍得到预防。作者提出了RAMP1可能是血管保护的重要介质和血管疾病的新治疗靶点的假设。一些研究报道，交感神经系统活性增强可能积极参与血管功能障碍的发病机制。在我们先前提出的一项研究中，在大鼠中枢神经系统中研究了CGRP诱导的去甲肾上腺素释放的变化。2.体外实验表明，CGRP以剂量依赖性方式抑制刺激诱发的去甲肾上腺素释放。二氢吡啶敏感性钙通道激动剂Bay K 8644可显著逆转CGRP对去甲肾上腺素释放的抑制作用，提示CGRP可能部分与二氢吡啶敏感性钙通道相互作用，调节细胞内钙动员。此外，我们发现，CGRP对去甲肾上腺素释放的抑制作用在自发性高血压大鼠与正常血压大鼠相比，显着减弱。3在外周组织中，Ohhashi和Rishbowitz 4观察到CGRP可能减少电刺激引起的大鼠输精管收缩，表明CGRP可能抑制肾上腺素能神经刺激时去甲肾上腺素的释放。CGRP的交感神经阻滞作用可能是对血管功能障碍的一种防御。由于血管紧张素II可能刺激中枢神经系统中的交感神经传递，5我们想知道交感神经活动的变化是否可能与RAMP1过表达的幅度有关，或者在Chrissobolis博士及其同事的研究中CGRP是否可能抑制血管紧张素II诱导的交感神经活动过度。CGRP和交感神经系统之间的相互作用及其在RAMP 1转基因小鼠血管紧张素II诱导的血管功能障碍中的保护作用有待进一步研究。
We read with great interest the recent article by Dr Chrissobolis and colleagues1 dealing with the cerebrovascular responses in the transgenic mice with overexpression of the receptor activitymodifying protein-1 (RAMP1) for calcitonin gene-related peptide (CGRP) receptors. The results of their study demonstrated that the responses to CGRP in carotid and basilar arteries in vitro as well as cerebral arterioles in vivo were selectively enhanced in human RAMP1 transgenic mice compared with controls. In addition, the authors presented that angiotensin II-induced oxidative stress and endothelial dysfunction was prevented after expression of RAMP1. The authors propose the hypothesis that RAMP1 may be an important mediator of vascular protection and a new therapeutic target in vascular disease. Several studies have reported that enhanced activity of the sympathetic nervous system might actively participate in the pathogenesis of vascular dysfunction. In a study we presented previously, the changes in norepinephrine release induced by CGRP was investigated in the rat central nervous system. 2 In an in vitro study, we showed that CGRP inhibited the stimulationevoked norepinephrine release in a dose-dependent manner. It was also demonstrated that a dihydropyridine-sensitive calcium channel agonist, Bay K 8644, significantly reversed the inhibitory effect of CGRP on norepinephrine release, indicating that CGRP might partially interact with dihydropyridine-sensitive calcium channels and modulate intracellular calcium mobilization. Furthermore, we showed that the inhibitory action on CGRP on norepinephrine release was significantly attenuated in spontaneously hypertensive rats compared with normotensive rats. 3 In the peripheral tissues, Ohhashi and Jacobowitz4 observed that CGRP might have reduced the electric stimulation-induced contraction of rat vas deferens, suggesting that CGRP might inhibit norepinephrine release during adrenergic nerve stimulation. It can be speculated that the sympatholytic action of CGRP might be a defense against vascular dysfunction. Because angiotensin II may stimulate the sympathetic neurotransmission in the central nervous system, 5 we would like to know whether changes in sympathetic nervous activity might be associated with the magnitude of the RAMP1 overexpression or whether CGRP might suppress the angiotensin II-induced sympathetic hyperactivity in the study of Dr Chrissobolis and colleagues. Further studies should be performed to assess more thoroughly the interactions between CGRP and the sympathetic nervous system and their role in the protective effect against the angiotensin II-induced vascular dysfunction in the RAMP1 transgenic mice.