REVERSING GLOMERULAR HYPERTENSION STABILIZES ESTABLISHED GLOMERULAR INJURY
REVERSING GLOMERULAR HYPERTENSION STABILIZES ESTABLISHED GLOMERULAR INJURY
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DOI：
10.1038/ki.1987.62
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发表时间：
1987-03-01
影响因子：
19.6
通讯作者：
BRENNER, BM
中科院分区：
文献类型：
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作者：
MEYER, TW;ANDERSON, S;BRENNER, BM
在5/6肾消融后18周对Munich-Wistar大鼠进行了研究。在未经处理的组I大鼠维持在标准的食物含有24%的蛋白质，持续的全身性和肾小球高血压与蛋白尿和广泛的肾小球损伤的增加。在第2组中，早期用转换酶抑制剂依那普利治疗可预防全身性和肾小球高血压，并在很大程度上限制蛋白尿和肾小球损伤。第3组和第4组在前8周内未接受治疗，在此期间，它们发生了全身性高血压和蛋白尿水平，这些蛋白尿水平先前显示与该时间点的显著肾小球硬化相关。依那普利治疗开始于第3组大鼠8周逆转全身和肾小球高血压，防止蛋白尿的进一步上升，并限制肾小球病变在18周相对于第1组。与第1组相比，第4组大鼠在第8周时将饮食蛋白含量降低至12%，可将肾小球但非全身性高血压控制至接近正常水平，稳定蛋白尿值，并在第18周时限制肾小球病变。这些研究支持了肾小球高血压是导致进行性肾小球损伤的一种重要血流动力学紊乱的观点。此外，即使治疗延迟至肾小球损伤建立，降低毛细血管压力也可以阻止残余肾小球损伤的进展。
Munich-Wistar rats were studied 18 weeks following 5/6 renal ablation. In untreated group I rats maintained on standard chow containing 24% protein, sustained systemic and glomerular hypertension were associated with increasing proteinuria and widespread glomerular injury. In group 2, early treatment with the converting enzyme inhibitor enalapril prevented systemic and glomerular hypertension, and largely limited proteinuria and glomerular injury. Groups 3 and 4 received no therapy during the first eight weeks, during which they developed systemic hypertension and levels of proteinuria previously shown to be associated with significant glomerular sclerosis at this time point. Enalapril therapy begun at eight weeks in group 3 rats reversed systemic and glomerular hypertension, prevented a further rise in proteinuria, and limited glomerular lesions at 18 weeks relative to group 1. Reduction of dietary protein content to 12% at eight weeks in group 4 rats controlled glomerular but not systemic hypertension to near-normal levels, stabilized proteinuria values, and also limited glomerular lesions at 18 weeks compared to group 1. These studies support the view that glomerular hypertension is an essential hemodynamic derangement responsible for progressive glomerular injury. Furthermore, reduction of capillary pressure can arrest the progression of remnant glomerular injury even when therapy is delayed until glomerular injury is established.