From the Department of Internal Medicine and Rehabilitation Science (S.Y., O.I., R.R., T.N., M.K.), Tohoku University Graduate School of Medicine, Japan.
Division of General Medicine and Rehabilitation (O.I.), Tohoku Medical and Pharmaceutical University Faculty of Medicine, Japan.
Hypertension. 2020 Jun;75(6):1447-1454. doi: 10.1161/HYPERTENSIONAHA.119.13905. Epub 2020 Apr 27.
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.
(P)RR（[pro] 肾素受体）被鉴定为肾素-血管紧张素系统的一个新组成部分。我们之前的研究报告表明，高盐（HS）摄入增加了 Sprague-Dawley 大鼠几个肾单位段的 (P)RR 表达。其他研究报告称，HS 摄入增加了黄嘌呤氧化酶（XO）活性，并且一种 MR（盐皮质激素受体）拮抗剂抑制了 Dahl 盐敏感（DS）大鼠肾脏中 HS 摄入增加的 (P)RR 表达。本研究检查了 HS 摄入对 DS 大鼠肾脏中 (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。一些喂食 HS 饮食的大鼠用 XO 抑制剂非布司他和 MR 拮抗剂螺内酯进行治疗。免疫印迹和免疫组织化学分析显示，HS 摄入使肾脏皮质中的 (P)RR 表达增加了 22.6 倍，使近端肾小管增加了 4.9 倍，使远端肾小管分别增加了 4.9 倍。非布司他和螺内酯均抑制了 HS 摄入增加的 (P)RR 表达在肾脏皮质中。非布司他抑制了 HS 摄入增加的 (P)RR 表达在近端肾小管中，而螺内酯抑制了 HS 摄入增加的 (P)RR 表达在远端肾小管中。此外，脱氧皮质酮乙酸盐增加了 DS 大鼠正常盐饮食中肾脏皮质和远端肾小管中的 (P)RR 表达，但未增加近端肾小管中的表达。这些结果表明，HS 摄入使 DS 大鼠肾脏皮质中的 (P)RR 表达大大增加。HS 摄入增加 (P)RR 表达的机制可能在近端肾小管中以 XO 依赖的方式起作用，在远端肾小管中以 MR 依赖的方式起作用。
