Jaenike J R
J Clin Invest. 1972 Dec;51(12):2999-3006. doi: 10.1172/JCI107127.
This study was designed to examine the pathogenesis of the excretory defect produced by bilateral ureteral obstruction in the rat. After release of obstruction of 24 hr duration glomerular filtration rate was reduced to 20% of normal. Free flow proximal tubular pressure was normal, excluding residual obstruction as a cause of depressed filtration, and indicating that an intrarenal hemodynamic abnormality was primarily responsible for the excretory defect. Total renal blood flow and cortical distribution of flow were normal. Clearance and micropuncture studies indicated the presence of marked heterogeneity of nephron function with residual excretory function residing primarily in vasodilated nephrons in which decreased postglomerular arteriolar resistance effected a reduction in glomerular filtration pressure. Heterogeneity of nephron function was evidenced by a wide scatter of values for single nephron filtration rate and from direct intratubular injection of dye which revealed that at least 28% of surface nephrons were either nonfiltering or had filtration rates too low to measure. The observed decrease in Hippuran extraction and increased ratio of Hippuran to inulin clearance ratio is characteristic of the vasodilated kidney. Further evidence of the vasodilated nature of residual functioning nephrons was demonstrated by the failure of intrarenal papaverine infusion to increase filtration rate in this lesion. The hemodynamic defect produced by bilateral obstruction is contrasted with that seen after release of unilateral ureteral ligation in which depression of filtration rate appears to result primarily from preglomerular vasoconstriction. This difference raises the possibility that a vasodilating substance accumulates during total suppression of renal excretory function. Diuresis and natriuresis were constant features of the postobstructive lesion. The present data support previously published studies which localize the defect in sodium transport to the distal nephron and indicate that this defect is a consequence of increased intraluminal pressure and tubular dilatation induced by bilateral ureteral ligation.
本研究旨在探讨大鼠双侧输尿管梗阻所致排泄缺陷的发病机制。在解除梗阻24小时后，肾小球滤过率降至正常的20%。自由流近端肾小管压力正常，排除了残余梗阻作为滤过降低的原因，表明肾内血流动力学异常是排泄缺陷的主要原因。肾总血流量和皮质血流分布正常。清除率和微穿刺研究表明，肾单位功能存在明显异质性，残余排泄功能主要存在于血管舒张的肾单位中，其中肾小球后小动脉阻力降低导致肾小球滤过压降低。单肾单位滤过率值广泛分散以及直接肾小管内注射染料显示至少28%的浅表肾单位不滤过或滤过率过低无法测量，证明了肾单位功能的异质性。观察到的马尿酸提取减少和马尿酸与菊粉清除率比值增加是血管舒张性肾脏的特征。肾内注射罂粟碱未能增加该病变的滤过率，进一步证明了残余功能肾单位的血管舒张性质。双侧梗阻产生的血流动力学缺陷与单侧输尿管结扎解除后所见的缺陷形成对比，单侧输尿管结扎解除后滤过率降低似乎主要是由于肾小球前血管收缩。这种差异增加了一种可能性，即在肾脏排泄功能完全受抑制期间，一种血管舒张物质会蓄积。利尿和利钠是梗阻后病变的持续特征。目前的数据支持先前发表的研究，这些研究将钠转运缺陷定位于远端肾单位，并表明该缺陷是双侧输尿管结扎引起的管腔内压力增加和肾小管扩张的结果。
