Ferrario C M, Chappell M C
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA.
Cell Mol Life Sci. 2004 Nov;61(21):2720-7. doi: 10.1007/s00018-004-4243-4.
Virtually all existing evidence on the function of angiotensin II (Ang II) in the regulation of tissue homeostasis and blood pressure regulation bears on the more restricted question of what other mechanisms or systems may amplify or inhibit the actions of this important peptide. Whereas there is evidence that Ang II may potentiate the effects of catecholamines, various cytokines and also growth factors, the repertoire of substances which may inhibit the actions of Ang II is more limited and has been restricted primarily to prostacyclin, bradykinin and nitric oxide. Advances in receptor pharmacology and introduction of selective antagonists to two of the receptor subtypes at which Ang II binds permitted a more critical examination of the functions of the renin angiotensin system in physiological and pathophysiological conditions, as well as uncovering the previously unsuspected possibility that within the biochemical pathways leading to the formation of the peptide the renin angiotensin system could process either its immediate precursor (angiotensin I) or the actual Ang II peptide into an alternative form, angiotensin-(1-7) [Ang-(1-7)], the function of which was to antagonize the effects of Ang II. We review here the biological actions of Ang-(1-7) and discuss how this discovery may change altogether the perception of how the renin angiotensin system functions in the regulation of tissue perfusion pressure and the regulation of salt and water metabolism.
几乎所有关于血管紧张素II（Ang II）在组织稳态调节和血压调节中功能的现有证据，都集中在一个更具局限性的问题上，即还有哪些其他机制或系统可能增强或抑制这种重要肽的作用。虽然有证据表明Ang II可能增强儿茶酚胺、各种细胞因子以及生长因子的作用，但可能抑制Ang II作用的物质种类更为有限，主要限于前列环素、缓激肽和一氧化氮。受体药理学的进展以及针对Ang II结合的两种受体亚型引入选择性拮抗剂，使得在生理和病理生理条件下对肾素血管紧张素系统的功能进行更严格的研究成为可能，同时也揭示了此前未曾预料到的可能性，即在导致该肽形成的生化途径中，肾素血管紧张素系统可能将其直接前体（血管紧张素I）或实际的Ang II肽加工成一种替代形式，即血管紧张素-（1-7）[Ang-（1-7）]，其功能是拮抗Ang II的作用。我们在此回顾Ang-（1-7）的生物学作用，并讨论这一发现可能如何彻底改变我们对肾素血管紧张素系统在组织灌注压调节以及盐和水代谢调节中功能的认识。
