A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats.
A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats.
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DOI：
10.1038/hr.2017.31
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Araie M
中科院分区：
文献类型：
--
作者：
Takahashi H;Nakagawa S;Wu Y;Kawabata Y;Numabe A;Yanagi Y;Tamaki Y;Uehara Y;Araie M
盐敏感性高血压与严重的器官损伤有关。产生氧自由基是盐引起的肾损伤的一个组成部分，活化的白细胞在氧自由基的生物合成中很重要。我们假设高盐饮食会导致免疫相关机制上调，从而导致达尔盐敏感大鼠对高血压肾损伤的易感性。为了验证这一假设，我们使用吖啶橙荧光镜和扫描激光检眼镜研究了当达尔盐敏感大鼠受到高盐（8％氯化钠）饮食挑战时粘附在视网膜血管上的白细胞。高盐饮食3天后增加了白细胞粘附力，并与肾脏中单核细胞趋化蛋白-1和细胞间粘附分子-1 (ICAM-1)相关分子的mRNA生物合成显着增加有关。在高盐负荷的早期高血压前期阶段，氯沙坦治疗不会影响白细胞粘附的增加；然而，氯沙坦在高血压阶段减弱了白细胞的粘附。此外，抗CD18抗体在高血压前期对白细胞粘附的抑制减少了白细胞的束缚，并与功能性和形态性肾损伤的减弱相关，而不影响血压升高。总之，高盐挑战通过 ICAM-1 的过度表达迅速增加了白细胞粘附。高血压前期白细胞粘附增加是达尔盐敏感大鼠随后肾损伤的原因。在盐诱发高血压的遗传模型中，免疫系统的参与可能是引发肾脏损伤的关键因素。
Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope. The high-salt diet increased leukocyte adhesion after 3 days and was associated with a significant increase in mRNA biosynthesis of monocyte chemotactic protein-1 and intercellular adhesion molecule-1 (ICAM-1) -related molecules in the kidney. Losartan treatment did not affect increased leukocyte adhesion during the early, pre-hypertensive phase of high salt loading; however, losartan attenuated the adhesion of leukocytes during the hypertensive stage. Moreover, the inhibition of leukocyte adhesion in the pre-hypertensive stage by anti-CD18 antibodies decreased tethering of leukocytes and was associated with the attenuation of functional and morphological kidney damage without affecting blood pressure elevation. In conclusion, a high-salt challenge rapidly increased leukocyte adhesion through the over-expression of ICAM-1. Increased leukocyte adhesion in the pre-hypertensive stage is responsible for subsequent kidney damage in Dahl salt-sensitive rats. Immune system involvement may be a key component that initiates kidney damage in a genetic model of salt-induced hypertension.
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影响因子：
82.9
作者：
Ishida, S;Yamashiro, K;Adamis, AP
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Adamis, AP
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