NEUROPHYSIOLOGICAL RESPONSES TO ANGIOTENSIN-(1-7)

NEUROPHYSIOLOGICAL RESPONSES TO ANGIOTENSIN-(1-7)
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DOI:
10.1161/01.hyp.17.6.1111
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发表时间:
1991-06-01
期刊:
影响因子:
8.3
通讯作者:
FERRARIO, CM
FERRARIO, CM
中科院分区:
医学1区
文献类型:
--
作者:
FELIX, D;KHOSLA, MC;FERRARIO, CM

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本研究的目的是用微离子电泳法研究七肽血管紧张素-(1-7)对室旁神经元自发活动的影响。最近的免疫细胞化学研究表明,这种血管紧张素I产物主要位于前脑和脑干的细胞和纤维中。我们的结果表明,血管紧张素-(1-7)在50-80nA的剂量下兴奋了室旁核的大部分神经元。与血管紧张素II或血管紧张素III相比,其起效时间和最大效应发生时间均明显延迟。随着血管紧张素-(1-7)剂量的增加,潜伏期缩短,放电频率呈剂量依赖性增加。在所有被测试的血管紧张素化合物中,血管紧张素III是最有效的。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亚型2拮抗剂CGP42112A阻断。因为大脑中的血管紧张素-(1-7)系统与中枢加压素能通路有关,所以用类似的方法测试了加压素。电泳法应用血管紧张素刺激的室旁核神经元对加压素的反应较弱。偶尔,也会观察到一种小的兴奋作用。我们的结果支持七肽血管紧张素-(1-7)是一种具有生物活性的神经肽的假说。这些数据还表明,血管紧张素II的氨基末端片段并不是不活跃的降解产物。
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.