Felix D, Khosla M C, Barnes K L, Imboden H, Montani B, Ferrario C M
Division of Neurobiology, University of Berne, Switzerland.
Hypertension. 1991 Jun;17(6 Pt 2):1111-4. doi: 10.1161/01.hyp.17.6.1111.
The aim of this study was to investigate the action of the heptapeptide angiotensin-(1-7) on the spontaneous activity of paraventricular neurons using microiontophoresis. Recent immunocytochemical investigations have shown that this product of angiotensin I is predominantly located in cells and fibers of the forebrain and brain stem. Our results show that most neurons in the paraventricular nucleus are excited by angiotensin-(1-7) at a dose of 50-80 nA. In comparison with angiotensin II or angiotensin III, the onset of response and the occurrence of the maximal effect were significantly delayed. With higher doses of angiotensin-(1-7), there was a decrease in latency and a dose-dependent increase in firing frequency. Of all the angiotensin compounds tested, angiotensin III was the most potent. Preliminary results obtained with an angiotensin antagonist show that the action of angiotensin II, angiotensin III, and angiotensin-(1-7) is blocked by the angiotensin receptor subtype 2 antagonist CGP 42112A. Because the angiotensin-(1-7) system in the brain is associated with central vasopressinergic pathways, vasopressin was tested in a similar way. Neurons in the paraventricular nucleus that were excited by iontophoretically applied angiotensins showed a weak response to vasopressin. Occasionally, a small excitatory action was observed. Our results support the hypothesis that the heptapeptide angiotensin-(1-7) is a biologically active neuropeptide. The data also suggest that amino terminal fragments of angiotensin II are not inactive degradation products.
本研究旨在利用微量离子电泳法研究七肽血管紧张素 -（1 - 7）对室旁核神经元自发放电活动的作用。最近的免疫细胞化学研究表明，血管紧张素I的这种产物主要位于前脑和脑干的细胞及纤维中。我们的结果显示，室旁核中的大多数神经元在50 - 80纳安的剂量下会被血管紧张素 -（1 - 7）兴奋。与血管紧张素II或血管紧张素III相比，反应的起始和最大效应的出现明显延迟。使用更高剂量的血管紧张素 -（1 - 7）时，潜伏期缩短，放电频率呈剂量依赖性增加。在所有测试的血管紧张素化合物中，血管紧张素III的作用最强。使用血管紧张素拮抗剂获得的初步结果表明，血管紧张素II、血管紧张素III和血管紧张素 -（1 - 7）的作用可被血管紧张素受体2亚型拮抗剂CGP 42112A阻断。由于脑中的血管紧张素 -（1 - 7）系统与中枢血管加压素能通路相关，因此以类似方式对血管加压素进行了测试。被离子电泳施加的血管紧张素兴奋的室旁核神经元对血管加压素反应较弱。偶尔会观察到轻微的兴奋作用。我们的结果支持七肽血管紧张素 -（1 - 7）是一种生物活性神经肽的假说。数据还表明血管紧张素II的氨基末端片段不是无活性的降解产物。
