Schurek H J, Aulbert E, Ebel H
Curr Probl Clin Biochem. 1976;6:281-90.
Evaluation of a possible role of NaK-ATPase in transtubular sodium reabsorption is difficult, since ouabain doses that inhibit this enzyme system in vitro completely [1, 11], cannot be applied in vivo. Thus studies in the isolated perfused rat kidney were carried out [3, 11, 13, 15]. However, in this model, supramaximal doses of ouabain as used to block NaK-ATPase completely induced a potent vasoconstriction, which lowers the filtered load of sodium. Thus, a meaningful quantitative comparison of sodium transport in control and in experimental phases of ouabain inhibition has not been possible. At submaximal doses, in which filtered Na-loads are still comparable, transport activity was only reduced to approximately 50% [15]. In the following experiments we reinvestigated the relationship between inhibition of renal NaK-ATPase and the reduction of Na-reabsorption by ouabain under more appropriate conditions. Previously we have observed that verapamil (syn.: iproveratril, Isoptin), a Ca ion antagonist [2, 4, 6], effectively prevents autoregulation, and a fact which is pertinent for the present experiments, blocks this vasoconstrictive action of ouabain. Thus, using the Ca antagonist verapamil, it was possible to evaluate the inhibiting effect of this glycoside on renal sodium transport quantitatively without the hazards introduced by ouabain vasoconstriction which by the same token lowers filtered load.
评估钠钾 - ATP酶在肾小管钠重吸收中可能发挥的作用存在困难，因为在体外能完全抑制该酶系统的哇巴因剂量[1,11]，无法在体内应用。因此，开展了对离体灌注大鼠肾脏的研究[3,11,13,15]。然而，在这个模型中，用于完全阻断钠钾 - ATP酶的超大剂量哇巴因会引发强烈的血管收缩，从而降低钠的滤过负荷。因此，无法对哇巴因抑制的对照阶段和实验阶段的钠转运进行有意义的定量比较。在亚最大剂量时，此时滤过的钠负荷仍具有可比性，转运活性仅降低至约50%[15]。在接下来的实验中，我们在更合适的条件下重新研究了肾钠钾 - ATP酶抑制与哇巴因导致的钠重吸收减少之间的关系。此前我们观察到，钙拮抗剂维拉帕米（同义词：异搏定，异搏停）[2,4,6]能有效阻止自身调节，并且与本实验相关的一个事实是，它能阻断哇巴因的这种血管收缩作用。因此，使用钙拮抗剂维拉帕米，就有可能定量评估这种糖苷对肾钠转运的抑制作用，而不会受到哇巴因血管收缩所带来的风险影响，因为同样的原因，哇巴因血管收缩会降低滤过负荷。
