Oxidative status in the macula densa modulates tubuloglomerular feedback responsiveness in angiotensin II-induced hypertension.
Oxidative status in the macula densa modulates tubuloglomerular feedback responsiveness in angiotensin II-induced hypertension.
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DOI：
10.1111/apha.12358
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Song J;Lu Y;Lai EY;Wei J;Wang L;Chandrashekar K;Wang S;Shen C;Juncos LA;Liu R
管肾小球反馈（Tubuloglomerular feedback， TGF）是控制信号肾元肾小球滤过率的重要机制。黄斑致密区氧化应激主要由一氧化氮（NO）和超氧化物（O2−）的相互作用决定，对维持TGF响应性至关重要。然而，在正常状态和高血压状态下，很少有研究研究黄斑致密区产生的NO和O2−的相互作用和数量。在本研究中，我们使用离体灌注的肾小球旁仪器直接测量生理和慢压血管紧张素II （Ang II）诱导的高血压小鼠黄斑致密区NO与O2−的相互作用。我们发现，剂量为600ng/kg/min的缓压药Ang II连续两周使平均动脉压升高26.1±5.7 mmHg。TGF反应由对照组的3.4±0.2 μm增加到高血压小鼠的5.2±0.2 μm。我们首先通过黄斑密度测量O2−的产生，发现在对照组小鼠中检测不到。然而，在angii诱导的高血压小鼠中，黄斑密度产生的O2−增加到21.4±2.5单位/分钟。然后我们测量了NO的生成量，发现对照组小鼠黄斑致密区NO生成量为138.5±9.3单位/分钟。注射Angⅱ后，高血压小鼠黄斑组织中未检测到NO。生理条件下，TGF反应主要受黄斑致密区产生的NO控制；在angii诱导的高血压中，TGF的反应主要受黄斑致密产生的O2−控制。
Tubuloglomerular feedback (TGF) is an important mechanism in control of signal nephron glomerular filtration rate. The oxidative stress in the macula densa, primarily determined by the interactions between nitric oxide (NO) and superoxide (O2−), is essential in maintaining the TGF responsiveness. However few studies examining the interactions between and amount of NO and O2− generated by the macula densa during normal and hypertensive states. In this study, we used isolated perfused juxtaglomerular apparatus to directly measure the amount and also studied the interactions between NO and O2− in macula densa in both physiological and slow pressor Angiotensin II (Ang II) induced hypertensive mice. We found that slow pressor Ang II at a dose of 600ng/kg/min for two weeks increased mean arterial pressure by 26.1±5.7 mmHg. TGF response increased from 3.4±0.2 μm in control to 5.2±0.2 μm in hypertensive mice. We first measured O2− generation by the macula densa and found it was undetectable in control mice. However, O2− generation by the macula densa increased to 21.4 ± 2.5 unit/min in Ang II-induced hypertensive mice. Then we measured NO generation and found that NO generation by the macula densa was 138.5 ± 9.3 unit/min in control mice. The NO was undetectable in the macula densa in hypertensive mice infused with Ang II. Under physiological conditions, TGF response is mainly controlled by the NO generated in the macula densa; in Ang II induced hypertension, the TGF response is mainly controlled by the O2− generated by the macula densa.
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DOI：
10.1161/hypertensionaha.111.184291
发表时间：
2012-02
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
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DOI：
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2009-01-01
影响因子：
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DOI：
10.1152/ajprenal.1999.277.1.f113
发表时间：
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