Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release.

Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release.
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DOI:
10.1161/01.hyp.19.2_suppl.ii41
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发表时间:
1992-02
期刊:
影响因子:
8.3
通讯作者:
D. Diz;Nancy T. Pirro
D. Diz;Nancy T. Pirro
中科院分区:
医学1区
文献类型:
--
作者:
D. Diz;Nancy T. Pirro

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血管紧张素II的中枢心血管和致渴效应涉及与去甲肾上腺素、多巴胺和5-羟色胺的相互作用。我们的研究结果表明,血管紧张素II受体和P物质的免疫反应性显示在背侧髓质的平行分布,血管紧张素II释放P物质从灌注大鼠髓质切片揭示了这些肽能系统之间的功能关系的潜力。其他证据表明,七肽血管紧张素-(1-7)通过选择性血管紧张素受体亚型发挥其生物学活性。因此,我们比较了这两种肽对77只雄性Sprague-Dawley大鼠延髓和下丘脑灌注切片中P物质和单胺类物质释放的影响。在用血管紧张素-(1-7)、血管紧张素II或单独的克雷布斯溶液(对照)灌注之前(基础)、期间(实验)和之后(恢复),在6分钟的灌注液收集中测定递质水平。P物质测定放射免疫法和单胺类及其代谢产物的高效液相色谱电化学检测。在实验期间,在髓质中,2 μ M血管紧张素II(但不是血管紧张素-(1-7))显着增加了P物质(基础值的221 +/- 87%)和去甲肾上腺素(基础值的130 +/- 17%)的流出。血管紧张素II对P物质的影响持续到恢复期。多巴胺及其代谢产物3,4-二羟基苯乙酸在该脑区未检测到。在下丘脑,血管紧张素-(1-7)和血管紧张素II均增加P物质(分别为基础值的169 +/- 30%和141 +/- 35%);血管紧张素II的作用在整个恢复期持续。(250字处删节)
The central cardiovascular and dipsogenic effects of angiotensin II involve interactions with norepinephrine, dopamine, and serotonin. Our findings that angiotensin II receptors and substance P immunoreactivity show a parallel distribution in the dorsal medulla and that angiotensin II releases substance P from perfused rat medulla slices revealed the potential for a functional relation between these peptidergic systems as well. Additional evidence suggests that the heptapeptide angiotensin-(1-7) exerts its biological activities via selective angiotensin receptor subtypes. Thus, we compared the effects of these two peptides on release of substance P and monoamines in perfused slices of medulla and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were determined in 6-minute collections of perfusate before (basal), during (experimental), and after (recovery) perfusion with either angiotensin-(1-7), angiotensin II, or Krebs' solution alone (control). Substance P was measured by radioimmunoassay and monoamines and their metabolites by high-performance liquid chromatography with electrochemical detection. In the medulla, 2 microM angiotensin II but not angiotensin-(1-7) significantly increased efflux of substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal) during the experimental period. The effect of angiotensin II on substance P was sustained into the recovery period. Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were not detected in this brain region. In the hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)