Bankir Lise, Chen Kai, Yang Baoxue
Cardiovascular Research Institute, University of California, 1246 Health Sciences East Tower, San Francisco, CA 94143-0521, USA.
Am J Physiol Renal Physiol. 2004 Jan;286(1):F144-51. doi: 10.1152/ajprenal.00205.2003. Epub 2003 Sep 9.
Recycling of urea within the renal medulla is known to play an important role in the capacity of the kidney to concentrate urine. This recycling occurs simultaneously through a tubular and a vascular route (i.e., through the loops of Henle and vasa recta, respectively). In the present study, transgenic mice with a selective deficiency in UT-B (the urea transporter protein expressed in descending vasa recta and red blood cells), were used to evaluate the specific contribution of vascular urea recycling to overall urine-concentrating ability (UCA). The renal handling of urea was studied in normal conditions and after acute or chronic alterations in urea excretion (acute urea loading or variations in protein intake, respectively). In normal conditions, UT-B null mice exhibited a 44% elevation in plasma urea (Purea), a normal creatinine clearance, but a 25% decrease in urea clearance, with no change in that of sodium and potassium. Acute urea loading induced a progressive increase in urinary urea concentration (Uurea) in wild-type mice and a subsequent improvement in their UCA in contrast to UT-B null mice, in which urinary osmolality and Uurea did not rise, due to the failure to accumulate urea in the medulla. With increasing protein intake (from 10 to 40% protein in diet, leading to a 5-fold increase in urea excretion), Purea was further increased in null mice while little change was observed in wild-type mice, and null mice were not able to increase Uurea as did wild-type mice. In conclusion, this study in UT-B-deficient mice reveals that countercurrent exchange of urea in renal medullary vessels and red blood cells accounts for a major part of the kidney's concentrating ability and for the adaptation of renal urea handling during a high-protein intake.
肾髓质内尿素的再循环在肾脏浓缩尿液的能力中起着重要作用,这一点已为人所知。这种再循环通过肾小管和血管两条途径同时发生(即分别通过髓袢和直小血管)。在本研究中,利用选择性缺乏UT-B(在直小血管降支和红细胞中表达的尿素转运蛋白)的转基因小鼠,来评估血管尿素再循环对整体尿液浓缩能力(UCA)的具体贡献。在正常条件下以及尿素排泄发生急性或慢性改变后(分别为急性尿素负荷或蛋白质摄入量变化),研究了尿素的肾脏处理情况。在正常条件下,UT-B基因敲除小鼠的血浆尿素(Purea)升高了44%,肌酐清除率正常,但尿素清除率下降了25%,而钠和钾的清除率没有变化。与UT-B基因敲除小鼠相比,急性尿素负荷使野生型小鼠的尿尿素浓度(Uurea)逐渐升高,随后其UCA得到改善,因为UT-B基因敲除小鼠由于髓质中无法积累尿素,尿渗透压和Uurea没有升高。随着蛋白质摄入量增加(饮食中蛋白质从10%增加到40%,导致尿素排泄增加5倍),基因敲除小鼠的Purea进一步升高,而野生型小鼠变化不大,并且基因敲除小鼠无法像野生型小鼠那样增加Uurea。总之,这项对UT-B缺陷小鼠的研究表明,肾髓质血管和红细胞中尿素的逆流交换占肾脏浓缩能力的主要部分,并且在高蛋白摄入期间参与了肾脏对尿素处理的适应性调节。