Schiavone M T, Khosla M C, Ferrario C M
Department of Brain and Vascular Research, Research Institute, Cleveland Clinic Foundation, OH 44195-5070.
J Cardiovasc Pharmacol. 1990;16 Suppl 4:S19-24.
Structure-activity studies of angiotensin II (Ang II) have clearly established that the carboxyl-terminal phenylalanine is crucial for activation of angiotensin receptors associated with a broad range of effects including vasoconstriction, aldosterone release, and dipsogenesis. Thus, the heptapeptide angiotensin-[1-7] (Ang-[1-7]) has been classified as an inactive metabolite of the hormone Ang II. This assumption was seriously questioned in light of the report from our laboratory that Ang-[1-7] is the major metabolite of dog brainstem homogenates both in the absence and in the presence of angiotensin-converting enzyme inhibitors. These data raised the possibility of a functional role for Ang-[1-7] in the brain. Subsequent studies in the in vitro hypothalamoneurohypophysial system of the rat demonstrated that Ang-[1-7] is equipotent with Ang II in its activation of AVP release. Other Ang II-like actions have since been identified for Ang-[1-7] in the brain. For example, microinjection of Ang-[1-7] into brainstem nuclei of the rat promotes bradycardia and hypotension; in addition, Ang-[1-7] mimics the effect of Ang II in augmenting the intrinsic discharge rate of neurons within the vagal-solitary complex of the dog. Our laboratory has also provided evidence for synthesis and storage of Ang-[1-7] in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
血管紧张素II（Ang II）的构效关系研究已明确证实，其羧基末端苯丙氨酸对于激活与多种效应相关的血管紧张素受体至关重要，这些效应包括血管收缩、醛固酮释放和饮水生成。因此，七肽血管紧张素-[1-7]（Ang-[1-7]）被归类为激素Ang II的无活性代谢产物。鉴于我们实验室的报告，即无论有无血管紧张素转换酶抑制剂，Ang-[1-7]都是犬脑干匀浆的主要代谢产物，这一假设受到了严重质疑。这些数据提出了Ang-[1-7]在大脑中具有功能作用的可能性。随后在大鼠体外下丘脑神经垂体系统中的研究表明，Ang-[1-7]在激活抗利尿激素释放方面与Ang II具有同等效力。此后，在大脑中还发现了Ang-[1-7]的其他类似Ang II的作用。例如，将Ang-[1-7]微量注射到大鼠脑干核中可促进心动过缓和低血压；此外，Ang-[1-7]在增强犬迷走神经-孤束复合体中神经元的固有放电率方面模拟了Ang II的作用。我们实验室也提供了大脑中Ang-[1-7]合成和储存的证据。（摘要截短于250字）
