Ichikawa I, Rennke H G, Hoyer J R, Badr K F, Schor N, Troy J L, Lechene C P, Brenner B M
J Clin Invest. 1983 Jan;71(1):91-103. doi: 10.1172/jci110756.
A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by approximately 30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PAN-perfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0.77 +/- 0.09 neq/min vs. 0.74 +/- 0.08, P greater than 0.40) and late portions of superficial distal tubules (0.31 +/- 0.02) neq/min vs. 0.32 +/- 0.05, P greater than 0.50), despite the lesser filtered load of sodium in PAN-perfused kidneys. Suppressed sodium reabsorption in both proximal convoluted tubules and short loops of Henle of PAN-perfused kidneys contributed to this equalization of sodium delivery rates to the late distal tubule, as did comparable reabsorption along distal convolutions. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, i.v.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.
为研究肾盐潴留的机制，在慕尼黑-维斯塔尔大鼠中建立了嘌呤霉素氨基核苷（PAN）诱导的单侧蛋白尿模型。在对左肾选择性灌注PAN（n = 8只大鼠）或等渗盐水（对照组，n = 7只大鼠）2周后，尽管全身血浆蛋白浓度维持在对照水平，但在接受PAN治疗的大鼠中，经PAN灌注的肾脏白蛋白排泄增加，钠排泄减少，而未灌注的肾脏则无此现象。经PAN灌注的肾脏总肾小球滤过率（GFR）和浅表单肾单位（SN）GFR也选择性降低，平均约降低30%，这主要是由于肾小球毛细血管超滤系数（Kf）显著下降，且这种下降也仅限于经PAN灌注的肾脏。经PAN灌注的肾脏中绝对近端重吸收（APR）值也选择性降低，这与这些肾脏中测得的肾小管周围毛细血管胶体渗透压的类似选择性下降一致，而后者也是Kf下降的结果。然而，在另一组7只接受PAN治疗的大鼠中，经PAN灌注和未灌注的肾脏在到达浅表远端小管早期（0.77±0.09纳摩尔/分钟对0.74±0.08，P>0.40）和晚期部分（0.31±0.02纳摩尔/分钟对0.32±0.05，P>0.50）的钠绝对量上未检测到差异，尽管经PAN灌注的肾脏中钠的滤过负荷较低。经PAN灌注的肾脏近端曲管和髓袢短袢中钠重吸收的抑制导致了向远端小管晚期钠输送速率的均衡，远端曲管的重吸收情况也类似。在另外两组接受PAN治疗的大鼠中，静脉输注沙拉新（0.3毫克/千克每小时）导致经PAN灌注的肾脏总肾GFR和SNGFR大幅增加，而未灌注的肾脏则无此现象。尽管总GFR和SNGFR有所增加，但经PAN灌注的肾脏尿钠排泄仍远低于未灌注的肾脏，这再次表明经PAN灌注的肾脏中钠排泄减少的特征是由于肾小管对钠的处理改变而非GFR变化所致。因此，这些结果表明：（a）在该模型中，Kf降低以及近端小管和髓袢段钠重吸收受抑制是由肾内因素而非循环或全身因素引起的；（b）假设浅表肾单位代表整个肾单位群体，该模型中的肾盐潴留主要是由于作用于远端曲管以外的肾内因素。
