Low Nitric Oxide Bioavailability Increases Renin Production in the Collecting Duct.
Low Nitric Oxide Bioavailability Increases Renin Production in the Collecting Duct.
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DOI：
10.3389/fphys.2020.559341
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发表时间：
2020
影响因子：
4
通讯作者：
Prieto MC
中科院分区：
文献类型：
--
作者：
Curnow AC;Gonsalez SR;Gogulamudi VR;Visniauskas B;Simon EE;Gonzalez AA;Majid DSA;Lara LS;Prieto MC
在肾脏中，集合管（CD-肾素）对肾素产生的刺激有助于高血压的发展。CD是合成一氧化氮（NO）的主要肾单位段，并且肾髓质中的低NO生物利用度与高血压相关。然而，目前还不清楚NO是否调节CD中的肾素产生。为了检验肾内低NO水平刺激CD-肾素产生的假设，我们首先检测了CD-eNOS缺陷小鼠远端肾单位段中的肾素表达。在这些小鼠中，特异性CD-肾素免疫反应性增加相比，野生型同窝仔，然而，肾小球（JG）肾素没有改变。为了进一步评估所涉及的细胞内机制，我们然后用1 mM L-NAME（L-精氨酸类似物）（一种NO合酶活性抑制剂）或1 mM NONOate（一种NO供体）处理M-1细胞。两种处理均增加了M-1细胞内的肾素蛋白水平。然而，只有抑制NOS与L-NAME刺激肾素合成和分泌所反映的Ren 1C转录和肾素蛋白水平的增加，在细胞外介质中，分别。此外，NONOate诱导cGMP的快速动员和细胞内肾素积累。ODQ（1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1]）抑制鸟苷酸环化酶可部分阻止这些反应。蛋白激酶G（PKG）和蛋白激酶C（PKC）抑制剂可阻断细胞内肾素的蓄积。我们的数据表明，低NO生物利用度增加CD-肾素的合成和分泌，这可能有助于肾内肾素血管紧张素系统的激活。
In the kidney, the stimulation of renin production by the collecting duct (CD-renin) contributes to the development of hypertension. The CD is a major nephron segment for the synthesis of nitric oxide (NO), and low NO bioavailability in the renal medulla is associated with hypertension. However, it is unknown whether NO regulates renin production in the CD. To test the hypothesis that low intrarenal NO levels stimulate the production of CD-renin, we first examined renin expression in the distal nephron segments of CD-eNOS deficient mice. In these mice, specific CD-renin immunoreactivity was increased compared to wild-type littermates; however, juxtaglomerular (JG) renin was not altered. To further assess the intracellular mechanisms involved, we then treated M-1 cells with either 1 mM L-NAME (L-arginine analog), an inhibitor of NO synthase activity, or 1 mM NONOate, a NO donor. Both treatments increased intracellular renin protein levels in M-1 cells. However, only the inhibition of NOS with L-NAME stimulated renin synthesis and secretion as reflected by the increase in Ren1C transcript and renin protein levels in the extracellular media, respectively. In addition, NONOate induced a fast mobilization of cGMP and intracellular renin accumulation. These response was partially prevented by guanylyl cyclase inhibition with ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1]. Accumulation of intracellular renin was blocked by protein kinase G (PKG) and protein kinase C (PKC) inhibitors. Our data indicate that low NO bioavailability increases CD-renin synthesis and secretion, which may contribute to the activation of intrarenal renin angiotensin system.
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DOI：
10.1152/ajprenal.00411.2018
发表时间：
2019-03-01
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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影响因子：
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10.1152/ajprenal.00360.2015
发表时间：
2016-02-15
影响因子：
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