Endothelium-derived nitric oxide supports renin cell recruitment through the nitric oxide-sensitive guanylate cyclase pathway.
Endothelium-derived nitric oxide supports renin cell recruitment through the nitric oxide-sensitive guanylate cyclase pathway.
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DOI：
10.1161/hypertensionaha.111.00221
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Kurtz A
中科院分区：
文献类型：
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作者：
Neubauer B;Machura K;Kettl R;Lopez ML;Friebe A;Kurtz A
慢性激发肾素-血管紧张素可引起肾脏中产生肾素的细胞沿着传入小动脉的中层聚集，肾小球体细胞肥大。本研究的目的是确定一氧化氮（NO）的作用方面的募集模式的肾素生产细胞和可能的途径沿着，NO可以发挥作用。我们认为内皮源性NO通过NO敏感的鸟苷酸环化酶起作用的假设。低盐饮食结合血管紧张素I转换酶抑制剂依那普利治疗小鼠3周，导致野生型小鼠的肾素表达增加13倍，与输入小动脉中的肾素细胞显著募集和肾小球体肥大相关。在野生型小鼠额外治疗的非选择性NO合酶抑制剂L-NAME，沿着传入小动脉的肾素表达细胞的招聘是不存在的，肾小球肥大减少。在缺乏内皮型NO合酶亚型的小鼠中，发现与野生型小鼠中L-NAME治疗几乎相同的肾素细胞募集衰减。用低盐饮食结合血管紧张素I转换酶抑制剂依那普利治疗缺乏一氧化氮敏感鸟苷酸环化酶的小鼠3周，可产生与野生型小鼠相似的肾小球肥大，但在传入小动脉中没有募集。这些结果表明，内皮源性NO和伴随形成的cGMP在肾小球前体细胞的肾素支持招聘的肾素表达细胞沿着肾小球前血管，但不是在肾小球装置。
Chronic challenge of renin–angiotensin causes recruitment of renin-producing cells in the kidney along the media layer of afferent arterioles and hypertrophy of cells in the juxtaglomerular apparatus. This study aimed to define the role of nitric oxide (NO) with regard to the recruitment pattern of renin-producing cells and to the possible pathways along which NO could act. We considered the hypothesis that endothelium-derived NO acts via NO-sensitive guanylate cyclase. Mice were treated with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks, which led to a 13-fold increase in renin expression associated with marked recruitment of renin cells in afferent arterioles and hypertrophy of the juxtaglomerular apparatus in wild-type mice. In wild-type mice additionally treated with the nonselective NO synthase inhibitor L-NAME, the recruitment of renin-expressing cells along the afferent arterioles was absent and juxtaglomerular hypertrophy was diminished. An almost identical attenuation of renin cell recruitment as with L-NAME treatment in wild-type mice was found in mice lacking the endothelial isoform of NO synthase. Treatment of mice lacking NO-sensitive guanylate cyclase in renin-expressing cells and preglomerular smooth muscle cells with low-salt diet in combination with the angiotensin I–converting enzyme inhibitor enalapril for 3 weeks produced juxtaglomerular hypertrophy like in wild-type mice, but no recruitment in afferent arterioles. These findings suggest that endothelium-derived NO and concomitant formation of cGMP in preglomerular renin cell precursors supports recruitment of renin-expressing cells along preglomerular vessels, but not in the juxtaglomerular apparatus.