Hillyard S D, Lu E, Gonick H C
Circ Res. 1976 Apr;38(4):250-5. doi: 10.1161/01.res.38.4.250.
Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
对容量扩张和缺水大鼠的肾脏煮沸匀浆进行柱色谱分析。将分配系数(Kav)在0.76 - 0.89范围内洗脱的组分(组分III)冻干,并评估这种半纯化制剂对离体蛙皮短路电流(SCC)、大鼠肾皮质钠钾ATP酶活性以及大鼠体内钠排泄的影响。在500微克/毫升的剂量下,容量扩张大鼠肾脏的组分III使SCC降低了21±5%(P<0.01),而缺水大鼠肾脏的相同组分使SCC产生了不显著的2±8%的变化。在剂量反应研究中,容量扩张大鼠肾脏的组分III,50、150、500和1500微克/毫升分别使SCC降低了4%、8%、19%和28%;500、1000和1500微克/毫升分别使钠钾ATP酶活性降低了11%、22%和49%。对缺水动物的组分III进行的相同研究在两种测定中均未显示出显著影响。此外,在组分III之后洗脱的容量扩张和缺水大鼠的组分(组分IV和V)对SCC或钠钾ATP酶活性没有影响。组分III在500微克/毫升的剂量下在体内也产生了显著的利钠作用,证实了我们的观察结果,即可以从容量扩张大鼠的肾脏中回收一种利钠物质。我们认为这种利钠物质可能通过抑制钠钾ATP酶来减少活性钠转运而起作用。