The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.

译文

血管活性肽的速激肽家族包括神经肽p物质,神经激肽A和神经激肽B,以及新发现的内收缩素和血收缩素。它们的心血管作用主要由神经激肽受体家族介导。这篇综述总结了了解速激肽对脉管系统影响的最新进展,并总结了它们的治疗潜力。速激肽刺激血浆外渗,特别是通过neurokinin-1受体以内皮依赖性方式起作用。因此,它们在组织水肿和炎症 (称为神经源性炎症) 中起着重要作用。速激肽的促炎作用通过刺激炎性细胞募集和启动血管生成的能力而增强。速激肽还调节血管张力和血流,尽管物种之间以及不同血管床之间的差异使这成为一个高度复杂的研究领域。在某些情况下,它们可能会放松血管,而在其他情况下会引起血管收缩,内皮状态似乎至关重要。速激肽还调节血压和心率,既作用于外周,又作用于中枢神经系统。速激肽和神经激肽受体的心血管作用可能是多种疾病 (例如肺水肿,高血压,先兆子痫,2型复杂区域疼痛综合征,中风和慢性炎症性疾病 (例如关节炎) 的重要治疗靶标。需要对人类疾病进行复杂的建模,以使神经激肽受体拮抗剂能够实现这种治疗潜力。

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