Recently, we reported a mutation in γ-Adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in FHH rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remains to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1^BN congenic rats (WT) with an intact myogenic response versus FHH 1^BN Add3KO (Add3KO) rats which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure (Pgc) rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After one week of hypertension, glomerular filtration rate (GFR) increased by 38%, and the glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a six-fold increase in Add3KO rats. The degree of renal injury was greater in Add3KO rats than WT rats after three weeks of hypertension. RBF, GFR, Pgc were lower by 20%, 28%, and 19% in Add3KO than WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.

中文翻译：

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受损的肾血流动力学和肾小球高滤过导致高血压引起的肾损伤。

最近，我们报道了 γ-Adducin (ADD3) 的突变与 FHH 大鼠传入小动脉和高血压诱导的慢性肾病 (CKD) 的肌源性反应受损有关。然而，改变的肾血流 (RBF) 自动调节促进高血压引起的肾损伤的机制仍有待确定。本研究比较了 FHH 1 ^BN同种大鼠 (WT) 与 FHH 1 ^BN相比，在具有完整肌源性反应的 DOCA 盐性高血压发展过程中肾脏血流动力学变化的时间过程和 CKD 的进展肌原性反应受损的 Add3KO (Add3KO) 大鼠。RBF 在 WT 大鼠中很好地自动调节，但在 Add3KO 大鼠中没有。当血压从 100 增加到 150 mmHg 时，WT 与 Add3KO 大鼠的肾小球毛细血管压力 (Pgc) 分别增加 6 和 14 mmHg。高血压治疗一周后，Add3KO 大鼠的肾小球滤过率 (GFR) 增加了 38%，肾小球 nephrin 表达降低了 20%。在 WT 大鼠中两者都没有改变。WT 大鼠的蛋白尿增加了一倍，而 Add3KO 大鼠的蛋白尿增加了 6 倍。高血压三周后，Add3KO 大鼠的肾损伤程度大于 WT 大鼠。在 Add3KO 中，RBF、GFR、Pgc 比 WT 大鼠低 20%、28% 和 19%，这与肾小球基质扩张和毛细血管滤过面积的损失有关。