Angiotensin II type 1 receptor blockade ameliorates tubulointerstitial injury induced by chronic potassium deficiency.
Angiotensin II type 1 receptor blockade ameliorates tubulointerstitial injury induced by chronic potassium deficiency.
复制标题
血管紧张素 II 1 型受体阻断可改善慢性缺钾引起的肾小管间质损伤。
DOI：
10.1046/j.1523-1755.2002.00208.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Johnson,RichardJ
中科院分区：
文献类型：
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作者：
Suga,Shin-Ichi;Mazzali,Marilda;Ray,PatricioE;Kang,Duk-Hee;Johnson,RichardJ
血管紧张素II 1型受体阻滞剂改善慢性钾缺乏引起的肾小管间质损伤。背景慢性钾（K+）缺乏是肾小管间质损伤的一个众所周知的原因，与血管活性介质的改变有关，包括持续产生肾皮质血管紧张素（Ang）II，尽管抑制血浆Ang II，和抑制尿亚硝酸盐/硝酸盐排泄。我们测试的假设，K+缺乏引起的肾小管间质损伤可以介导的血管紧张素II或减少在nitricoxide.MethodsRats喂养K+缺乏饮食（0.01%K+）单独，或与氯沙坦或L-精氨酸（L-Arg）在饮用水。对照组大鼠饲喂正常K+饲料（0.36%K+）。在10周结束时，肾脏被切除，肾损伤evaluated.ResultsSerum K+在所有三个组接受K+缺乏饮食同样沮丧。仅缺钾饮食的大鼠出现肾脏肥大和肾小管间质纤维化，肾小管骨桥蛋白表达增加，巨噬细胞浸润和III型胶原沉积。氯沙坦的管理显着减少肾脏肥大，并防止肾小管间质损伤的皮质，虽然一些髓质损伤发生。与此相反，L-Arg的管理并没有减弱肾小管间质损伤的皮质，尽管完全恢复尿硝酸盐排泄。轻度，但显着的改善肾小管骨桥蛋白的表达和巨噬细胞浸润中观察到的髓质L-Arg-治疗hypokalemic rats.ConclusionsThese结果表明，低钾肾损伤介导的，至少部分，通过血管紧张素II 1型受体，与一氧化氮减少介导的贡献较小。氯沙坦可能有助于预防低钾性肾小管间质损伤。
Angiotensin II type 1 receptor blockade ameliorates tubulointerstitial injury induced by chronic potassium deficiency.BackgroundChronic potassium (K+) deficiency, one of the well-known causes of renal tubulointerstitial injury, is associated with an alteration in vasoactive mediators including persistent generation of renal cortical angiotensin (Ang) II despite the suppression of plasma Ang II, and suppression of urinary nitrite/nitrate excretion. We tested the hypothesis that K+-deficiency–induced renal tubulointerstitial injury could be mediated by Ang II or a reduction in nitric oxide.MethodsRats were fed a K+-deficient diet (0.01% K+) alone, or with either losartan orL-arginine (L-Arg) in drinking water. Control rats were fed with a normal K+diet (0.36% K+). At the end of 10 weeks, kidneys were excised and renal injury was evaluated.ResultsSerum K+was similarly depressed in all three groups receiving the K+-deficient diet. Rats on the K+-deficient diet alone developed renal hypertrophy and tubulointerstitial fibrosis with an increase in tubular osteopontin expression, macrophage infiltration and type III collagen deposition. Administration of losartan significantly reduced renal hypertrophy and prevented tubulointerstitial injury in the cortex, although some medullary injury occurred. In contrast, administration of L-Arg did not attenuate tubulointerstitial injury in the cortex, despite a complete recovery of urinary nitrate excretion. Mild but significant improvement of tubular osteopontin expression and macrophage infiltration were observed in the medulla of L-Arg-treated hypokalemic rats.ConclusionsThese results indicate that hypokalemic renal injury is mediated, at least in part, by Ang II via the Ang II type 1 receptor, with a lesser contribution mediated by a reduction in nitric oxide. Losartan may be beneficial in preventing hypokalemic tubulointerstitial injury.