Thomas S R
INSERM U. 323, Faculté de Mèdecine Necker, Paris, France.
Bull Math Biol. 1991;53(6):825-43. doi: 10.1007/BF02461486.
Modelling studies have played an important role in research on the mechanism of urine concentration and dilution by the medulla of the kidney ever since Hargitay and Kuhn (1951, Z. Elektrochem. 55, 539-558) first proposed that the parallel tubular structures in the kidney medulla must function as a "countercurrent multiplication" system. Present-day models, in keeping with our considerably improved understanding of most aspects of medullary structure-function relationships, have evolved into rather sophisticated systems of parallel tubes. In spite of this increasing complexity, it has remained the case that "model medullas" do not concentrate as well as the real kidney, especially in the inner medulla where only passive, diffusional transport occurs. Inasmuch as these models take into account the majority of contemporary ideas making up our global hypothesis about the functioning of this system, their failure to behave physiologically indicates that our understanding remains incomplete. The purpose of the present modelling study was to evaluate the implications of some recent measurements showing that permeabilities of NaCl (Ps) and urea (Pu) vary along the length of the descending thin limbs of Henle (Imai et al., 1988, Am. J. Physiol. 254, F323-F328), rather than being constant throughout this segment as had been assumed earlier. It was hoped that these newly measured values might explain, by a passive, diffusional process, the net solute addition at the bend of Henle's loop observed under some circumstances and heretofore attributed (though without any supporting experimental evidence) to active transport into the descending limb. The results of the present study show that whereas incorporation of the new values for Ps and Pu in the descending limbs of short nephrons does indeed improve the concentrating power of the model, these new values are nonetheless not sufficient to allow the model to build an osmolarity gradient that increases all the way through the inner medulla. This failing, which is common to virtually all modelling studies to date using measured values from rat kidneys, probably points to a key role for preferential exchange supposed by some to exist among certain tubule segments within vascular bundles in species whose kidneys have the highest concentrating power.
自从哈吉泰伊和库恩(1951年,《电化学杂志》55卷,539 - 558页)首次提出肾髓质中的平行管状结构必定起着“逆流倍增”系统的作用以来,模型研究在肾脏髓质尿液浓缩和稀释机制的研究中发挥了重要作用。如今的模型,与我们对髓质结构 - 功能关系大多数方面有了显著改善的理解相一致,已经发展成为相当复杂的平行管系统。尽管复杂性不断增加,但“模型髓质”的浓缩能力仍不如真实肾脏,尤其是在仅发生被动扩散转运的内髓质。由于这些模型考虑了构成我们关于该系统功能的整体假设的大多数当代观点,它们在生理行为上的失败表明我们的理解仍然不完整。本模型研究的目的是评估一些近期测量结果的影响,这些测量结果表明氯化钠(Ps)和尿素(Pu)的通透性沿亨利袢降支细段的长度而变化(今井等人,1988年,《美国生理学杂志》254卷,F323 - F328页),而不是像早期所假设的那样在该段全程保持恒定。人们希望这些新测量的值可能通过被动扩散过程解释在某些情况下在亨利袢弯曲处观察到的净溶质添加,此前一直将其归因于(尽管没有任何支持性实验证据)主动转运进入降支。本研究结果表明,虽然在短肾单位的降支中纳入Ps和Pu的新值确实提高了模型的浓缩能力,但这些新值仍然不足以使模型构建一个贯穿内髓质一直增加的渗透压梯度。这种失败几乎是迄今为止所有使用大鼠肾脏测量值的模型研究所共有的,这可能表明在具有最高浓缩能力的物种的血管束内某些肾小管段之间存在一些人所认为的优先交换的关键作用。