Zhang Y, Mircheff A K, Hensley C B, Magyar C E, Warnock D G, Chambrey R, Yip K P, Marsh D J, Holstein-Rathlou N H, McDonough A A
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
Am J Physiol. 1996 Jun;270(6 Pt 2):F1004-14. doi: 10.1152/ajprenal.1996.270.6.F1004.
Acute arterial hypertension provokes a rapid decrease in proximal tubule (PT) Na+ reabsorption, increasing flow to the macula densa, the signal for tubuloglomerular feedback. We tested the hypothesis, in rats, that Na+ transport is decreased due to rapid redistribution of apical Na+/H+ exchangers and basolateral Na+ pumps to internal membranes. Arterial pressure was increased 50 mmHg by constricting various arteries. We also tested whether transporter internalization occurred when PT Na+ reabsorption was inhibited with the carbonic anhydrase inhibitor benzolamide. Five minutes after initiating either natriuretic stimuli, cortex was removed, and membranes were fractionated by density gradient centrifugation. Urine output and endogenous lithium clearance increased threefold in response to either stimuli. Acute hypertension provoked a redistribution of apical Na+/H+ exchanger NHE3, alkaline phosphatase, and dipeptidyl peptidase IV to higher density membranes enriched in the intracellular membrane markers. Basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity decreased 50%, 25-30% of the alpha 1-and beta 1-subunits redistributed to higher density membranes, and the remainder is attributed to decreased activity of the transporters. Benzolamide did not alter Na+ transporter activity or distribution, implying that decreasing apical Na+ uptake does not initiate redistribution or inhibition of basolateral Na(+)-K(+)-ATPase. We conclude that PT natriuresis provoked by acute arterial pressure is mediated by both endocytic removal of apical Na+/H+ exchangers and basolateral Na+ pumps as well as decreased total Na+ pump activity.
急性动脉高血压可导致近端小管（PT）对钠离子重吸收迅速减少，增加致密斑处的流量，致密斑是管球反馈的信号。我们在大鼠中验证了这样一个假说，即钠离子转运减少是由于顶端钠离子/氢离子交换体和基底外侧钠离子泵迅速重新分布到内膜所致。通过收缩不同动脉使动脉压升高50 mmHg。我们还测试了用碳酸酐酶抑制剂苯并酰胺抑制近端小管钠离子重吸收时，转运体是否会发生内化。在开始利尿刺激5分钟后，取出皮质，通过密度梯度离心对膜进行分级分离。两种刺激均使尿量和内源性锂清除率增加了三倍。急性高血压促使顶端钠离子/氢离子交换体NHE3、碱性磷酸酶和二肽基肽酶IV重新分布到富含细胞内膜标记物的更高密度膜中。基底外侧膜钠钾腺苷三磷酸酶（Na(+)-K(+)-ATPase）活性降低了50%，α1和β1亚基的25%-30%重新分布到更高密度膜中，其余归因于转运体活性降低。苯并酰胺未改变钠离子转运体活性或分布，这意味着减少顶端钠离子摄取不会引发基底外侧钠钾腺苷三磷酸酶的重新分布或抑制。我们得出结论，急性动脉压引起的近端小管利钠作用是由顶端钠离子/氢离子交换体和基底外侧钠离子泵的内吞清除以及总钠泵活性降低介导的。
