High Salt Intake-Increased (Pro)renin Receptor Expression Is Exaggerated in the Kidney of Dahl Salt-Sensitive Rats
High Salt Intake-Increased (Pro)renin Receptor Expression Is Exaggerated in the Kidney of Dahl Salt-Sensitive Rats
复制标题
Dahl 盐敏感大鼠肾脏中高盐摄入增加肾素 (Pro) 受体表达过度
DOI：
10.1161/hypertensionaha.119.13905
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发表时间：
2020
期刊：
影响因子：
8.3
通讯作者：
Kohzuki Masahiro
中科院分区：
文献类型：
--
作者：
Yamakoshi Seiko;Ito Osamu;Rong Rong;Ohsaki Yusuke;Nakamura Takahiro;Hirose Takuo;Takahashi Kazuhiro;Mori Takefumi;Totsune Kazuhito;Kohzuki Masahiro
（P）RR（[原]肾素受体）被确定为肾素-血管紧张素系统的一个新的组成部分。我们先前报道了高盐（HS）摄入增加了Sprague-Dawley大鼠几个肾单位节段的（P）RR表达。其他研究报告HS摄入增加XO（黄嘌呤氧化酶）活性，MR（盐皮质激素受体）拮抗剂抑制HS摄入增加（P）RR表达在达尔盐敏感（DS）大鼠的肾脏。本研究检测了HS摄入对DS大鼠肾脏（P）RR表达的影响。雄性DS大鼠喂食正常盐饮食或HS饮食4周。用XO抑制剂非布司他和MR拮抗剂螺内酯处理饲喂HS饲料的一些大鼠。免疫印迹和免疫组化分析显示，HS摄入使肾皮质的RR表达增加了22.6倍，近端小管增加了4.9倍，远端小管增加了4.9倍。非布司他和螺内酯均抑制肾皮质中HS摄入增加（P）RR表达。非布司他抑制近端小管中HS摄入增加（P）RR表达，而螺内酯抑制远端小管中HS摄入增加（P）RR表达。此外，醋酸脱氧皮质酮增加（P）RR表达在肾皮质和远端小管，但不是在近端小管的DS大鼠喂养正常的盐饮食。这些结果表明，HS摄入大大增加（P）RR表达在DS大鼠的肾皮质。HS摄入增加（P）RR表达的机制可能在近端小管中以XO依赖性方式起作用，在远端小管中以MR依赖性方式起作用。
The (P)RR ([pro]renin receptor) was identified as a new component of the renin-angiotensin system. We previously reported that high salt (HS) intake increased the (P)RR expression in several nephron segments of Sprague-Dawley rats. Other studies reported HS intake increased the XO (xanthine oxidase) activity and an MR (mineralocorticoid receptor) antagonist inhibited HS intake–increased (P)RR expression in the kidneys of Dahl salt-sensitive (DS) rats. The present study examined the effects of HS intake on (P)RR expression in the kidney of DS rats. Male DS rats were fed a normal salt diet or an HS diet for 4 weeks. Some of the rats fed on the HS diet were treated with the XO inhibitor, febuxostat, and the MR antagonist, spironolactone. Immunoblot and immunohistochemical analyses showed that HS intake increased (P)RR expression in the renal cortex by 22.6-fold, the proximal tubules by 4.9-fold and the distal tubules, respectively. Both febuxostat and spironolactone inhibited HS intake–increased (P)RR expression in the renal cortex. Febuxostat inhibited HS intake–increased (P)RR expression in the proximal tubules, whereas spironolactone inhibited HS intake–increased (P)RR expression in the distal tubules. Additionally, deoxycorticosterone acetate increased (P)RR expression in the renal cortex and distal tubules but not in the proximal tubules of DS rats fed the normal salt diet. These results indicate that HS intake greatly increases (P)RR expression in the renal cortex of DS rats. The mechanisms of HS intake–increased (P)RR expression may work in an XO-dependent manner in the proximal tubules and an MR-dependent manner in the distal tubules.