Li Chunling, Wang Weidong, Kwon Tae-Hwan, Knepper Mark A, Nielsen Søren, Frøkiaer Jørgen
The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark.
Am J Physiol Renal Physiol. 2003 Nov;285(5):F889-901. doi: 10.1152/ajprenal.00170.2003. Epub 2003 Jul 15.
Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na+/H+ exchanger (NHE3) to 41 +/- 14%, type 2 Na-Pi cotransporter (NaPi-2) to 26 +/- 6%, Na-K-ATPase to 67 +/- 8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20 +/- 7%, and thiazide-sensitive cotransporter (TSC) to 37 +/- 9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53 +/- 10%, NaPi-2 to 57 +/- 9%, Na-K-ATPase to 62 +/- 8%, BSC-1 to 50 +/- 12%, and TSC to 56 +/- 16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616 +/- 54 vs. 944 +/- 24 micromol x min-1 x kg-1; P < 0.05) and phosphate (6.3 +/- 0.9 vs. 13.1 +/- 0.4 micromol x min-1. kg-1; P < 0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria.
尿路梗阻会损害尿液浓缩能力和钠的重吸收。为了阐明这些缺陷的分子机制，我们检测了双侧输尿管梗阻（BUO）24小时的大鼠、或解除BUO（BUO-R）后第3天或第14天大鼠肾脏钠转运体的表达水平。BUO导致3型钠氢交换体（NHE3）下调至41±14%，2型钠磷共转运体（NaPi-2）下调至26±6%，钠钾ATP酶下调至67±8%，1型布美他尼敏感型钠钾2氯共转运体（BSC-1）下调至20±7%，噻嗪敏感型共转运体（TSC）下调至37±9%。免疫细胞化学证实了NHE3、NaPi-2、钠钾ATP酶、BSC-1和TSC的下调。与这种下调一致，BUO-R与多尿、尿渗透压降低以及尿钠和磷酸盐排泄增加有关。BUO-R持续3天导致NHE3持续下调至53±10%，NaPi-2下调至57±9%，钠钾ATP酶下调至62±8%，BSC-1下调至50±12%，TSC下调至56±16%，这与肾脏钠的净重吸收（616±54对944±24微摩尔·分钟-1·千克-1；P<0.05）和磷酸盐（6.3±0.9对13.1±0.4微摩尔·分钟-1·千克-1；P<0.05）显著降低相关，表明肾脏钠和磷酸盐重吸收能力存在缺陷。此外，钠钾ATP酶和TSC的下调在BUO-R持续14天时仍然存在，而NHE3、NaPi-2和BSC-1恢复至对照水平。总之，BUO大鼠和解除BUO后肾脏钠转运体的下调可能导致相关的尿液浓缩缺陷、尿钠排泄增加和梗阻后多尿。
