Overexpression of eNOS prevents the development of renovascular hypertension in mice
Overexpression of eNOS prevents the development of renovascular hypertension in mice
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DOI：
10.1139/y08-044
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发表时间：
2008-07-01
影响因子：
2.1
通讯作者：
Meyrelles, Silvana S.
中科院分区：
文献类型：
--
作者：
Gava, Agata L.;Peotta, Veronica A.;Meyrelles, Silvana S.
基因治疗已成为了解多种心血管疾病的重要工具。在本研究中，我们研究了内皮一氧化氮合酶（eNOS）过表达在肾血管性高血压中的作用。实验将C57BL/6小鼠随机分为两肾一夹（2K1C）高血压组和假手术组。在进行手术的同时，2K1C小鼠和假手术小鼠均静脉注射表达功能基因eNOS或报告基因β -半乳糖苷酶（β -gal）的重组腺病毒。14天后，对有意识小鼠的动脉压、压力反射敏感性、心脏交感神经和副交感神经张力进行评估。平均动脉压测量显示，与sham-beta - gal小鼠相比，2K1C-beta - gal小鼠的动脉高血压（121 +/- 3比96 +/- 2 min Hg， p < 0.01），这是由eNOS过表达（2K1C-eNOS 100 4比sham-eNOS 99 3 mm Hg）阻止的。对硝普钠诱导的低血压的反射性心动过速的线性回归分析显示，2k1c - β - gal小鼠的压力反射敏感性显著减弱（5.8 +/- 0.5 vs. sham- β - gal 8.0 +/- 0.8 beat.min (-1).mm Hg-1, p < 0.05），但这种减弱并没有被eNOS过表达（2K1C-eNOS 7.2 +/- 0.5 vs. sham-eNOS）所阻止。8.8 +/- 0.7 beats.min(-1).mm Hg-1, p < 0.05)。2k1c - β gal（152 +/- 17和45 +/- 12次）心跳时，心脏交感神经张力增强，迷走神经张力降低。Min（-1）分别与假β - gal小鼠（112 +/- 6和89 +/- 7次）相比。min(-1))，与sham-eNOS相比，2K1C-eNOS小鼠也观察到类似的结果。数据表明，eNOS过表达能够阻止小鼠2K1C肾血管性高血压的发展，而不影响其他特征性心血管功能障碍。
Gene therapy has become an important tool for understanding several cardiovascular diseases. In the present study we investigated the effects of endothelial nitric oxide synthase (eNOS) overexpression on renovascular hypertension. Experiments were carried out in C57BL/6 mice randomly assigned to either a two-kidney one-clip (2K1C) hypertension group or a sham-operated group. At the same time surgery was carried out, both 2K1C and sham mice received an intravenous injection of recombinant adenovirus expressing the functional gene eNOS or the reporter gene beta-galactosidase (beta-gal). Fourteen days later, arterial pressure, baroreflex sensitivity, and cardiac sympathetic and parasympathetic tone were evaluated in conscious mice. Measurement of mean arterial pressure showed arterial hypertension in 2K1C-beta gal mice compared with sham-beta gal mice (121 +/- 3 vs. 96 +/- 2 min Hg, p < 0.01), which was prevented by eNOS overexpression (2K1C-eNOS 100 4 vs. sham-eNOS 99 3 mm Hg). Linear regression analysis of the reflex tachycardia response to sodium nitroprusside-induced hypotension showed that baroreflex sensitivity was significantly attenuated in 2K1C-beta gal mice (5.8 +/- 0.5 vs. sham-beta gal 8.0 +/- 0.8 beats.min(-1).mm Hg-1, p < 0.05), but this decrease was not prevented by eNOS overexpression (2K1C-eNOS 7.2 +/- 0.5 vs. sham-eNOS. 8.8 +/- 0.7 beats.min(-1).mm Hg-1, p < 0.05). The cardiac sympathetic tone was augmented and the vagal tone was reduced in 2K1C-beta gal (152 +/- 17 and 45 +/- 12 beats.min(-1), respectively) compared with sham-beta gal mice (112 +/- 6 and 89 +/- 7 beats.min(-1), respectively), and similar results were observed in 2K1C-eNOS mice compared with sham-eNOS. The data indicate that eNOS overexpression was able to prevent the development of 2K1C renovascular hypertension in mice, without affecting other characteristic cardiovascular dysfunctions.