Effect of potassium concentration and ouabain on the renal adaptation to potassium depletion in isolated perfused rat kidney

Renal adaptation for potassium (K) conservation has been demonstrated in isolated perfused kidneys from rats within 3 days of K depletion and appears to be independent of aldosterone and sodium excretion. This study was designed to investigate whether the renal adaptation for K conservation is independent of ambient [K] and renal tissue levels of K and whether ouabain may have effects on K excretion, which are in constrast to the effects on K excretion in normal animals, in the first study, rats K depleted for 3 days received 2500 μequiv. KCl intraperitoneally, while other K-depleted rats and a group of control diet animals received intraperitoneal H2O alone to determine whether simple restoration of K deficits would reverse the renal adaptation for K conservation. Intraperitoneal KCl increased plasma [K] and kidney tissue K significantly within 3 h in the K-repleted group compared with the K-depleted rats. Isolated kidneys were perfused from the three groups of rats 3 h after intraperitoneal injection. Despite K repletion in vivo, perfused kidneys from the K-repleted group still had significantly decreased K excretion (1.28 ± 0.085 μequiv./min) compared with controls (2.05 ± 0.291 μequiv./min), and K excretion was still not different from the K-depleted group (0.57 ± 0.134 μequiv./min). However, fractional K excretion by the kidneys from K-repleted rats was increased above K-depleted kidneys (0.48 ± 0.051 vs. 0.18 ± 0.034, p < 0.01). Despite the increased renal tissue K in K-repleted kidneys at the start of perfusion (285 ± 5.1 vs. 257 ± 5.4 μequiv./g), by the end of the perfusion tissue K in perfused kidneys was identical in all three groups. In the second study, isolated kidneys were perfused from 3-day K-depleted or control rats with either 2 or 6 mM [K] in the perfusate. Isolated kidneys adapted to 3 days of K depletion excreted less K at both 2 and 6 mM [K] compared with controls at the same ambient [K]. The linear relationship of K excretion to perfusate [K] was significantly different in controls compared with low K adapted kidneys (p < 0.001). Finally, when 10−4 M ouabain was added after 60 min of perfusion in kidneys from control diet rats, there was a sodium diuresis and fractional K excretion decreased significantly (0.55 ± 0.043 to 0.32 ± 0.044, p < 0.01). However, in low K adapted kidneys, ouabain had no effect on fractional K excretion (0.020 ± 0.051 to 0.18 ± 0.038) despite a similar increase in sodium excretion. Perfusions of kidneys from 3-day K-depleted rats at 4 × 10−3 M ouabain gave similar results, showing no change in fractional K excretion. Low K adaptation to K depletion developed within 3 days and was not totally abolished by acute K repletion. Maneuvers that favored either a decrease in renal tissue K or an increase in tissue K did not reverse low K adaptation, although renal tissue K levels did alter the rate of K excretion in both controls and K-depleted kidneys. Therefore, a reduction in tissue K was clearly not the sole mediator of renal K conservation. Finally, the markedly different response of low K adapted kidneys to ouabain compared with controls strongly suggests a mechanism for K reabsorption that developed within 3 days of K depletion and is ouabain sensitive.