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首页> 外文期刊>American Journal of Physiology >Nuclear angiotensin-(1-7) receptor is functionally coupled to the formation of nitric oxide.
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Nuclear angiotensin-(1-7) receptor is functionally coupled to the formation of nitric oxide.

机译：核血管紧张素-（1-7）受体在功能上与一氧化氮的形成有关。

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The kidney is an important target for the actions of the renin-angiotensin system (RAS) and this tissue contains a complete local RAS that expresses the bioactive peptides angiotensin II (ANG II) and Ang-(1-7). We find both angiotensin type 1 (AT(1)R) and type 2 (AT(2)R) receptors expressed on renal nuclei that stimulate reactive oxygen species and nitric oxide (NO), respectively. Since Ang-(1-7) also exhibits actions within the kidney and the Ang-(1-7)/Mas receptor protein contains a nuclear localization sequence, we determined the expression of Ang-(1-7) receptors in nuclei isolated from the kidneys of young adult sheep. Binding studies with (125)I-[Sar(1)Thr(8)]-ANG II revealed sites sensitive to the Ang-(1-7) antagonist [d-Ala(7)]-Ang-(1-7) (DALA, A779), as well as to AT(2) and AT(1) antagonists. Incubation of Ang-(1-7) [10(-15) to 10(-9) M] with isolated cortical nuclei elicited a dose-dependent increase in the fluorescence of the NO indicator [4-amino-5-methylamino-2',7']-difluorofluorescein diacetate. The NO response to Ang-(1-7) was abolished by the NO inhibitor N-nitro-l-arginine methyl ester and DALA, but not the AT(1) antagonist losartan or the AT(2) blocker PD123319. Immunofluorescent studies utilizing the Ang-(1-7)/Mas receptor antibody revealed immunolabeling of the proximal tubules but not staining within the glomerulus in cortical sections of the sheep kidney. In the nuclear fraction of isolated proximal tubules, immunoblots revealed the precursor angiotensinogen and renin, as well as functional activity for ACE, ACE2, and neprilysin. We conclude that renal nuclei express Ang-(1-7)/Mas receptors that are functionally linked to NO formation. The marked sensitivity of the intracellular NO response to Ang-(1-7) implicates a functional role of the Ang-(1-7) axis within the nucleus. Moreover, evidence for the precursor and enzymatic components of the RAS within the nuclear compartment of the proximal tubules provides a potential pathway for the intracellular generation of Ang-(1-7).
机译：肾脏是肾素-血管紧张素系统（RAS）作用的重要靶标，并且该组织包含表达生物活性肽血管紧张素II（ANG II）和Ang-（1-7）的完整局部RAS。我们发现血管紧张素1型（AT（1）R）和2型（AT（2）R）受体表达在肾核上分别刺激活性氧和一氧化氮（NO）。由于Ang-（1-7）还在肾脏内发挥作用，并且Ang-（1-7）/ Mas受体蛋白包含核定位序列，因此我们确定了Ang-（1-7）受体在分离自细胞核中的表达年轻成年绵羊的肾脏。与（125）I- [Sar（1）Thr（8）]-ANG II的结合研究揭示了对Ang-（1-7）拮抗剂[d-Ala（7）]-Ang-（1-7）敏感的位点（DALA，A779），以及AT（2）和AT（1）拮抗剂。用分离的皮层核温育Ang-（1-7）[10（-15）到10（-9）M]引起NO指示剂[4-amino-5-methylamino-2]的荧光剂量依赖性增加。 '，7']-二氟荧光素二乙酸盐。 NO抑制剂N-硝基-1-精氨酸甲酯和DALA消除了对Ang-（1-7）的NO反应，但没有消除AT（1）拮抗剂氯沙坦或AT（2）阻滞剂PD123319。利用Ang-（1-7）/ Mas受体抗体进行的免疫荧光研究显示，羊肾皮质部分的肾小球内未进行近端小管的免疫标记，但未染色。在分离的近端小管的核部分中，免疫印迹显示了前体血管紧张素原和肾素以及对ACE，ACE2和中性溶酶的功能活性。我们得出的结论是，肾核表达Ang-（1-7）/ Mas受体，这些受体功能上与NO形成有关。细胞内NO对Ang-（1-7）的显着敏感性暗示着Ang-（1-7）轴在细胞核内的功能。此外，近端小管核室内RAS的前体和酶成分的证据为Ang-（1-7）的细胞内生成提供了潜在途径。

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