Layton H E, Knepper M A, Chou C L
Department of Mathematics, Duke University, Durham, North Carolina 27708-0320, USA.
Am J Physiol. 1996 Jan;270(1 Pt 2):F9-20. doi: 10.1152/ajprenal.1996.270.1.F9.
The urine concentrating effect of the mammalian renal inner medulla has been attributed to countercurrent multiplication of a transepithelial osmotic difference arising from passive absorption of NaCl from thin ascending limbs of long loops of Henle. This study assesses, both mathematically and experimentally, whether the permeability criteria for effective function of this passive hypothesis are consistent with transport properties measured in long loops of Henle of chinchilla. Mathematical simulations incorporating loop of Henle transepithelial permeabilities idealized for the passive hypothesis generated a steep inner medullary osmotic gradient, confirming the fundamental feasibility of the passive hypothesis. However, when permeabilities measured in chinchilla were used, no inner medullary gradient was generated. A key parameter in the apparent failure of the passive hypothesis is the long-loop descending limb (LDL) urea permeability, which must be small to prevent significant transepithelial urea flux into inner medullary LDL. Consequently, experiments in isolated perfused thin LDL were conducted to determine whether the urea permeability may be lower under conditions more nearly resembling those in the inner medulla. LDL segments were dissected from 30-70% of the distance along the inner medullary axis of the chinchilla kidney. The factors tested were NaCl concentration (125-400 mM in perfusate and bath), urea concentration (5-500 mM in perfusate and bath), calcium concentration (2-8 mM in perfusate and bath), and protamine concentration (300 micrograms/ml in perfusate). None of these factors significantly altered the measured urea permeability, which exceeded 20 x 10(-5) cm/s for all conditions. Simulation results show that this moderately high urea permeability in LDL is an order of magnitude too high for effective operation of the passive countercurrent multiplier.
哺乳动物肾内髓的尿液浓缩作用归因于亨利氏袢长襻细段升支对NaCl的被动重吸收所产生的跨上皮渗透压差的逆流倍增。本研究通过数学和实验方法评估了这一被动假说有效发挥作用的通透性标准是否与在灰鼠亨利氏袢长襻中测得的转运特性相一致。纳入了针对被动假说理想化的亨利氏袢跨上皮通透性的数学模拟产生了陡峭的内髓渗透梯度，证实了被动假说的基本可行性。然而，当使用在灰鼠中测得的通透性时，并未产生内髓梯度。被动假说明显失效的一个关键参数是长襻降支（LDL）的尿素通透性，它必须很小以防止大量的跨上皮尿素通量进入内髓LDL。因此，进行了分离灌注的细LDL实验，以确定在更接近内髓条件下尿素通透性是否可能更低。从灰鼠肾脏内髓轴30% - 70%距离处分离出LDL段。所测试的因素包括NaCl浓度（灌注液和浴液中为125 - 400 mM）、尿素浓度（灌注液和浴液中为5 - 500 mM）、钙浓度（灌注液和浴液中为2 - 8 mM）以及鱼精蛋白浓度（灌注液中为300微克/毫升）。这些因素均未显著改变所测得的尿素通透性，在所有条件下该通透性均超过20×10⁻⁵厘米/秒。模拟结果表明，LDL中这种适度较高的尿素通透性对于被动逆流倍增器的有效运作而言高了一个数量级。
