BHF Centre of Cardiovascular Excellence and Centre for Integrative Biomedicine, Cardiovascular Division, Franklin-Wilkins Building, Waterloo Campus, King's College London, London SE19NH, UK.
Neuropeptides. 2011 Apr;45(2):93-104. doi: 10.1016/j.npep.2010.12.002. Epub 2011 Jan 26.
Hypertension is still presently the number one "silent killer" in the Western World, and a major risk factor for the development of secondary diseases contributing to cardiovascular disease (CVD). However, despite a broad range of therapies, the mechanisms involved in the onset of hypertension remains unclear, therefore there is a real need to investigate the mechanisms involved. Calcitonin gene-related peptide (CGRP) is the most potent microvascular vasodilator known to date. Widely expressed in the nervous system, this peptide is considered to play a positive role in wound healing and protects against ischaemic and other traumas. However, whilst the protective mechanisms are not well understood, evidence indicates that these mechanisms become important in vascular-related stress. This review provides evidence that CGRP is both a potent vasodilator and hypotensive agent. However studies to date suggest that CGRP does not contribute to the physiological regulation of blood pressure. By comparing results from a range of human and animal studies, findings broadly suggest an association between CGRP and the pathophysiology of hypertension in terms of protective mechanisms, with possibly the RAMP1 component of the CGRP receptor playing a key role in the brain stem, in addition to peripheral receptors. The studies of agents that release CGRP agonists are at an early stage, with analogues for human use currently under development. However, at this stage, further research is required to establish the mechanisms by which CGRP is protective in the onset of hypertension, if novel and therapeutic modes of treatment are to be developed.
高血压目前仍然是西方世界头号“无声杀手”，也是导致心血管疾病（CVD）的继发性疾病的主要危险因素之一。然而，尽管有广泛的治疗方法，高血压发病的机制仍不清楚，因此有必要研究相关机制。降钙素基因相关肽（CGRP）是迄今为止已知的最有效的微血管血管扩张剂。该肽在神经系统中广泛表达，被认为在伤口愈合中发挥积极作用，并能预防缺血和其他创伤。然而，尽管保护机制尚不清楚，但有证据表明，这些机制在与血管相关的应激中变得重要。这篇综述提供了证据表明 CGRP 既是一种有效的血管扩张剂又是一种降压剂。然而，迄今为止的研究表明，CGRP 并不参与血压的生理调节。通过比较一系列人类和动物研究的结果，研究结果普遍表明 CGRP 与高血压的病理生理学之间存在关联，特别是 CGRP 受体的 RAMP1 成分在脑干中可能发挥关键作用，而外周受体也是如此。释放 CGRP 激动剂的药物研究仍处于早期阶段，目前正在开发用于人类的类似物。然而，在现阶段，如果要开发新的治疗模式，需要进一步研究 CGRP 在高血压发病中的保护机制。
