Bodineau Laurence, Frugière Alain, Marc Yannick, Claperon Cédric, Llorens-Cortes Catherine
U 691, Inserm, 11, Place Marcelin Berthelot, Paris Cedex 05, France.
Heart Fail Rev. 2008 Sep;13(3):311-9. doi: 10.1007/s10741-007-9077-3. Epub 2008 Jan 3.
Among the main bioactive peptides of the brain renin-angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for the type 1 and type 2 Ang receptors. Both peptides, injected intracerebroventricularly, cause similar increase in blood pressure (BP). Because AngII is converted in vivo to AngIII, the identity of the true effector is unknown. This review summarized recent insights into the predominant role of brain AngIII in the central control of BP underlining the fact that brain aminopeptidase A (APA), the enzyme forming central AngIII, could constitute a putative central therapeutic target for the treatment of hypertension. This led to the development of potent, systematically active APA inhibitors, such as RB150, as a prototype of a new class of centrally acting antihypertensive agents for the treatment of certain forms of hypertension.
在脑肾素-血管紧张素系统的主要生物活性肽中，血管紧张素（Ang）II和AngIII对1型和2型Ang受体表现出相同的亲和力。两种肽经脑室内注射后，会引起相似的血压（BP）升高。由于AngII在体内会转化为AngIII，因此真正的效应物身份尚不清楚。本综述总结了近期关于脑AngIII在血压中枢控制中的主要作用的见解，强调了这样一个事实，即形成中枢AngIII的酶——脑氨肽酶A（APA），可能构成治疗高血压的一个假定的中枢治疗靶点。这促使人们开发出了强效的、具有全身活性的APA抑制剂，如RB150，作为一类新型中枢性抗高血压药物的原型，用于治疗某些类型的高血压。
