Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, Nordstjernevej 42, DK-2600, Glostrup, Denmark.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Oe, Denmark.
Eur J Pharmacol. 2020 Aug 15;881:173205. doi: 10.1016/j.ejphar.2020.173205. Epub 2020 May 19.
Vascular tissue consists of endothelial cells, vasoactive smooth muscle cells and perivascular nerves. The perivascular sensory neuropeptide CGRP has demonstrated potent vasodilatory effects in any arterial vasculature examined so far, and a local protective CGRP-circuit of sensory nerve terminal CGRP release and smooth muscle cell CGRP action is evident. The significant vasodilatory effect has shadowed multiple other effects of CGRP in the vascular tissue and we therefore thoroughly review vascular actions of CGRP on endothelial cells, vascular smooth muscle cells and perivascular nerve terminals. The actions beyond vasodilation includes neuronal re-uptake and neuromodulation, angiogenic, proliferative and antiproliferative, pro- and anti-inflammatory actions which vary depending on the target cell and anatomical location. In addition to the classical perivascular nerve-smooth muscle CGRP circuit, we review existing evidence for a shadowed endothelial autocrine pathway for CGRP. Finally, we discuss the impact of local and systemic actions of CGRP in vascular regulation and protection from hypertensive and ischemic heart conditions with special focus on therapeutic CGRP agonists and antagonists.
血管组织由内皮细胞、血管活性平滑肌细胞和血管周围神经组成。迄今为止，在所有检查过的动脉血管中，血管周围感觉神经肽 CGRP 表现出强大的血管舒张作用，并且可以明显看出感觉神经末梢 CGRP 释放和平滑肌细胞 CGRP 作用的局部保护 CGRP 回路。CGRP 在血管组织中的这种显著的血管舒张作用掩盖了其多种其他作用，因此我们彻底回顾了 CGRP 对内皮细胞、血管平滑肌细胞和血管周围神经末梢的血管作用。除了血管舒张作用之外，CGRP 的作用还包括神经元再摄取和神经调节、血管生成、增殖和抗增殖、促炎和抗炎作用，这些作用因靶细胞和解剖位置而异。除了经典的血管周围神经-平滑肌 CGRP 回路外，我们还回顾了 CGRP 存在的被掩盖的内皮细胞自分泌途径的现有证据。最后，我们讨论了 CGRP 在血管调节和高血压及缺血性心脏病保护中的局部和全身作用的影响，特别关注治疗性 CGRP 激动剂和拮抗剂。
