INSERM U872, Paris.
Curr Pharm Des. 2011;17(25):2654-62. doi: 10.2174/138161211797416002.
A fair amount of data indicates that bradykinin and lysyl-bradykinin exert arterial, cardiac and renal effects which afford protection against organ damage in diseases, especially in the settings of ischemia or diabetes. The concept of kinins acting as therapeutic agents is supported by the wide use of angiotensin I-converting enzyme (ACE) inhibitors. These inhibitors indeed potentiate kinin action by inhibiting kinin degradation. Experimental evidence strongly suggests that the cardiac and renal effects of ACE inhibitors are due, at least in part, to kinins. Angiotensin AT1 receptor antagonists act also partly through kinins. This paper reviews available evidence supporting a role for kinins in the therapeutic effect of current drugs. It then discusses the opportunity to develop new drugs based on kinin action. Direct activation of the kinin B2 receptor by pharmacological agonists might provide higher therapeutic benefit than existing kinin- potentiating drugs. Possible occurrence of side effects is however a concern.
相当多的数据表明缓激肽和赖氨酰缓激肽对动脉、心脏和肾脏具有保护作用,可防止疾病(特别是在缺血或糖尿病的情况下)引起的器官损伤。激肽作为治疗剂的概念得到了广泛使用血管紧张素转化酶(ACE)抑制剂的支持。这些抑制剂通过抑制激肽降解确实增强了激肽的作用。实验证据强烈表明,ACE 抑制剂的心脏和肾脏作用至少部分归因于激肽。血管紧张素 AT1 受体拮抗剂也部分通过激肽起作用。本文综述了支持激肽在现有药物治疗效果中发挥作用的现有证据。然后讨论了基于激肽作用开发新药的机会。药理学激动剂对激肽 B2 受体的直接激活可能比现有的激肽增强药物提供更高的治疗益处。然而,可能会出现副作用。