Speth Robert C, Karamyan Vardan T
Department of Pharmacology and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi, MS 38677, USA.
Heart Fail Rev. 2008 Sep;13(3):299-309. doi: 10.1007/s10741-007-9078-2. Epub 2008 Jan 9.
From the outset, the concept of a brain renin-angiotensin system (RAS) has been controversial and this controversy continues to this day. In addition to the unresolved questions as to the means by which, and location(s) where brain Ang II is synthesized, and the uncertainties regarding the functionality of the different subtypes of Ang II receptors in the brain, a new controversy has arisen with respect to the identity of the angiotensin peptide(s) that activate brain AT(1) receptors. While it has been known for some time that Ang III can activate Ang II receptors with equivalent or near-equivalent efficacy to Ang II, it has been proposed that in the brain, only Ang III is active. This proposal, which we have named "The Angiotensin III Hypothesis" states that Ang II must be converted to Ang III in order to activate brain AT(1) receptors. This review examines several aspects of the controversies regarding the brain RAS with a special focus on brain aminopeptidases, studies that either support or refute The Angiotensin III Hypothesis, and the implications of The Angiotensin III Hypothesis for the activity of the brain RAS. It also addresses the need for further research that can test The Angiotensin III Hypothesis and definitively identify the angiotensin peptide(s) that activate brain AT(1) receptor-mediated effects.
从一开始，脑肾素-血管紧张素系统（RAS）的概念就存在争议，并且这种争议一直持续到今天。除了关于脑内血管紧张素II（Ang II）的合成方式和位置等尚未解决的问题，以及脑内不同亚型的Ang II受体功能的不确定性之外，关于激活脑内AT(1)受体的血管紧张素肽的身份又出现了新的争议。虽然人们早就知道Ang III可以以与Ang II相当或近乎相当的效力激活Ang II受体，但有人提出，在脑内只有Ang III具有活性。我们将这一观点命名为“血管紧张素III假说”，该假说认为Ang II必须转化为Ang III才能激活脑内AT(1)受体。这篇综述探讨了关于脑RAS争议的几个方面，特别关注脑氨肽酶、支持或反驳血管紧张素III假说的研究，以及血管紧张素III假说对脑RAS活性的影响。它还阐述了进一步研究的必要性，这些研究能够检验血管紧张素III假说，并明确鉴定出激活脑内AT(1)受体介导效应的血管紧张素肽。
