Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition
Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition
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DOI：
10.1681/asn.2013091030
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发表时间：
2014-12-01
影响因子：
13.6
通讯作者：
Gonzalez-Villalobos, Romer A.
中科院分区：
文献类型：
--
作者：
Giani, Jorge F.;Janjulia, Tea;Gonzalez-Villalobos, Romer A.
肾脏是包括人类在内的许多物种血管紧张素转换酶（ACE）的重要来源。然而，局部ACE对肾功能的具体影响，进而对血压控制的影响尚不完全清楚。我们之前的研究表明，缺乏肾ACE的小鼠对血管紧张素II输注引起的高血压有抵抗性。在这里，我们检测了这些小鼠对L-NAME抑制一氧化氮合成的低系统性血管紧张素II高血压模型的反应。与野生型小鼠相比，没有肾ACE的小鼠没有发生高血压，肾血管紧张素II水平较低，L-NAME对钠尿的反应增强。在L-NAME治疗期间，肾脏ACE的缺失与GFR反应减弱有关；近端小管Na+/H+交换体3、Na+/Pi共转运体2、磷酸化Na+/K+/Cl-共转运体和磷酸化Na+/Cl-共转运体的丰度显著降低；以及上皮Na+通道γ亚型的丰度和加工的更大减少。总之，肾组织中ACE的存在促进了血管紧张素II的积累、GFR的降低、钠转运体的表达水平和翻译后修饰的变化，而钠转运体是对一氧化氮合成抑制的钠潴存和高血压所必需的。
The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na+/H+ exchanger 3, Na+/Pi co-transporter 2, phosphorylated Na+/K+/Cl- cotransporter, and phosphorylated Na+/Cl- cotransporter; and greater reductions in abundance and processing of the gamma isoform of the epithelial Na+ channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition.