Whiteside C I, Lumsden C J
Department of Medicine, University of Toronto, Ontario, Canada.
Am J Physiol. 1989 May;256(5 Pt 2):F882-93. doi: 10.1152/ajprenal.1989.256.5.F882.
Glomerular polyanion function was explored using charged and neutral [3H]dextrans in the multiple indicator-dilution experiment. Anesthetized dogs received an intrarenal bolus of 125I-labeled albumin (plasma reference), [14C]inulin (glomerular reference) and [3H]dextran (test solute), followed by rapid serial sampling of the renal venous and urine outflows. Reduced urinary recovery of cationic diethylaminoethyl dextrans (DEAE) [3H]dextrans [19.0- to 31.5-A Stokes-Einstein radius (SER)], compared with neutral [3H]dextran indicated intrarenal binding reversed by excess unlabeled cationic dextran. Tubular microperfusion with cationic [3H]dextran confirmed a pretubular binding site (presumed glomerular). The application of a computer-assisted mathematical model of convective flux plus reversible binding revealed that binding affinity increased with molecular size. In vitro high-affinity binding of the same cationic [3H]dextrans to isolated rat glomeruli was also found to increase with molecular size and was inhibited by protamine sulfate. Intrarenal polycation perfusion with protamine sulfate (1.0-3.8 mg/g kidney) or lysozyme (1.1-2.2 mg/g body wt) resulted in intraglomerular binding of anionic [3H]dextran without increased proteinuria or altered glomerular permselectivity to neutral [3H]dextrans less than or equal to 33.0-A SER. Hence, transglomerular cationic solute flux is mediated by a convection-binding mechanism that creates an effective polyvalent barrier.
在多指示剂稀释实验中，使用带电荷和中性的[³H]葡聚糖来探究肾小球多阴离子功能。对麻醉犬进行肾内推注¹²⁵I标记的白蛋白（血浆参考物）、[¹⁴C]菊粉（肾小球参考物）和[³H]葡聚糖（测试溶质），随后对肾静脉流出液和尿液进行快速连续采样。与中性[³H]葡聚糖相比，阳离子二乙氨基乙基葡聚糖（DEAE）[³H]葡聚糖[斯托克斯 - 爱因斯坦半径（SER）为19.0至31.5 Å]的尿回收率降低，表明肾内结合可被过量未标记的阳离子葡聚糖逆转。用阳离子[³H]葡聚糖进行肾小管微灌注证实了肾小管前结合位点（推测为肾小球）。应用对流通量加可逆结合的计算机辅助数学模型表明，结合亲和力随分子大小增加。还发现相同的阳离子[³H]葡聚糖与分离的大鼠肾小球的体外高亲和力结合也随分子大小增加，并被硫酸鱼精蛋白抑制。用硫酸鱼精蛋白（1.0 - 3.8 mg/g肾脏）或溶菌酶（1.1 - 2.2 mg/g体重）进行肾内聚阳离子灌注导致阴离子[³H]葡聚糖在肾小球内结合，而蛋白尿未增加，对SER小于或等于33.0 Å的中性[³H]葡聚糖的肾小球通透选择性也未改变。因此，跨肾小球阳离子溶质通量由对流 - 结合机制介导，该机制形成了有效的多价屏障。
