Yates N A, McDougall J G
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Vic., Australia.
Ren Physiol Biochem. 1995 Nov-Dec;18(6):311-20. doi: 10.1159/000173932.
Evidence exists that an endogenous substance which inhibits (Na+,K+)-ATPase, in a similar manner to the cardiac glycosides, may have important cardiovascular and renal effects. Whilst ouabain or a closely related isomer has been reported to be present in mammalian plasma, renal effects of ouabain occur only at high concentrations. The effect of expansion of blood volume on the renal response to ouabain infusion was examined in conscious sheep. Five sheep with catheters chronically implanted into the renal artery received four treatment combinations in random order: (I) vehicle (0.15 mol l-1 NaCl) infusion; (II) 500 micrograms ouabain infused into the renal artery over 60 min; (III) 500 ml 6% dextran 70 in 0.9% saline infused intravenously, and (IV) the dextran and ouabain treatments together. Treatment with either ouabain or plasma volume expansion produced modest increases in sodium excretion and urine flow. Treatment with ouabain when combined with plasma volume expansion increased sodium excretion from 82 +/- 30 to 880 +/- 203 mumol min-1 and urine flow from 1.9 +/- 1.1 to 7.5 +/- 1.6 ml min-1. This combination of treatments results in a synergistic rather than additive response. This study indicates that under some circumstances the response of the kidney to inhibition of (Na+,K+)-ATPase can be enhanced and, if inhibition can be demonstrated to occur at physiologically relevant concentrations of endogenous digitalis-like factor, would support a possible physiological role for endogenous digitalis-like factor in the regulation of sodium homeostasis.
有证据表明，一种内源性物质以与强心苷类似的方式抑制（Na⁺，K⁺）-ATP酶，可能具有重要的心血管和肾脏效应。虽然已报道哇巴因或一种密切相关的异构体存在于哺乳动物血浆中，但哇巴因的肾脏效应仅在高浓度时才会出现。在清醒的绵羊中研究了血容量扩张对肾脏对哇巴因输注反应的影响。五只长期将导管植入肾动脉的绵羊按随机顺序接受四种处理组合：（I）输注载体（0.15 mol l⁻¹ NaCl）；（II）在60分钟内将500微克哇巴因注入肾动脉；（III）静脉输注500 ml含6%右旋糖酐70的0.9%盐水，以及（IV）右旋糖酐和哇巴因联合处理。单独使用哇巴因或血浆容量扩张处理均使钠排泄和尿流量有适度增加。当哇巴因与血浆容量扩张联合使用时，钠排泄从82±30增加到880±203 μmol min⁻¹，尿流量从1.9±1.1增加到7.5±1.6 ml min⁻¹。这种处理组合导致协同而非相加反应。本研究表明，在某些情况下，肾脏对（Na⁺，K⁺）-ATP酶抑制的反应可以增强，如果能证明抑制作用发生在内源性洋地黄样因子的生理相关浓度下，将支持内源性洋地黄样因子在钠稳态调节中可能的生理作用。
