Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Berlin, Germany.
Expert Opin Emerg Drugs. 2011 Dec;16(4):619-30. doi: 10.1517/14728214.2011.618495. Epub 2011 Sep 12.
The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels.
The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology.
Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.
肾素-血管紧张素-醛固酮系统(RAAS)已经是心血管系统药物最重要的靶点。然而,仍有新的进展旨在在不同层面上干扰该系统。
干扰 RAAS 的新策略旨在减少两种主要 RAAS 效应激素血管紧张素(Ang)II 和醛固酮的合成,或分别干扰它们的受体 AT1 和盐皮质激素受体。此外,RAAS 中的新靶点已被确定,如(前)肾素受体,以及对抗 Ang II 经典作用的分子,因此对心血管疾病有益。这些包括 AT2 受体和 ACE2/Ang-(1-7)/Mas 轴。因此,寻找激活 RAAS 这些组织保护分支的药物是 RAAS 药理学中最具创新性的领域。
大多数抑制经典 RAAS 的新型药理学策略需要在临床试验中证明其优于现有治疗方法,然后在竞争激烈的市场中与这些现已相当便宜的药物竞争。新发现的靶点具有超越心血管系统的功能,为干扰 RAAS 成分的药物开辟了新的治疗领域。