Ferrario C M, Santos R A, Brosnihan K B, Block C H, Schiavone M T, Khosla M C, Greene L J
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5070.
Clin Exp Hypertens A. 1988;10 Suppl 1:107-21. doi: 10.3109/10641968809075966.
Studies of the in vivo and in vitro metabolism of angiotensin peptide precursors, and of angiotensin II (Ang II) in tissues, has revealed the possibility that some of the fragments formed through specific enzymatic pathways are bioactive. There is evidence that Ang III is as potent as Ang II in stimulating thirst and causing aldosterone secretion. New findings from this laboratory have led us to reevaluate the concept that fragments of angiotensins derived from the amino (N-) terminus are devoid of biological activity. Using in vitro and in vivo techniques, we showed that Ang-(1-7) is processed from Ang I in amounts equal to or greater than Ang II. In addition, Ang-(1-7) generation is not dependent upon Ang I converting enzyme (ACE) activity in homogenates of canine brain stem. This heptapeptide promotes release of vasopressin from perifused hypothalamo-neurohypophysial explant and stimulates neural responses when microinjected into the vagal-solitary complex. The data supporting these findings are discussed below.
对血管紧张素肽前体的体内和体外代谢以及组织中血管紧张素II（Ang II）的研究表明，通过特定酶促途径形成的一些片段可能具有生物活性。有证据表明，血管紧张素III（Ang III）在刺激口渴和引起醛固酮分泌方面与血管紧张素II一样有效。本实验室的新发现促使我们重新评估源自氨基（N-）末端的血管紧张素片段缺乏生物活性这一概念。使用体外和体内技术，我们发现血管紧张素（1-7）（Ang-(1-7)）从血管紧张素I（Ang I）加工而来的量等于或大于血管紧张素II。此外，在犬脑干匀浆中，血管紧张素（1-7）的生成不依赖于血管紧张素I转换酶（ACE）的活性。这种七肽促进血管加压素从灌流的下丘脑-神经垂体外植体中释放出来，并在微量注射到迷走神经-孤束复合体中时刺激神经反应。支持这些发现的数据将在下面讨论。
