Modulation of renal sodium-potassium-adenosine triphosphatase by aldosterone. Effect of high physiologic levels on enzyme activity in isolated rat and rabbit tubules.

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Abstract

The purpose of this study was to determine the nephron site, time course, and mechanism of mineralocorticoid action on renal tubular Na-K-ATPase in rats and rabbits, without dietary manipulation and by using the natural mineralocorticoid aldosterone. Sustained, high physiologic levels of circulating aldosterone mimicking those produced endogenously during potassium loading or sodium deprivation were provided by constant delivery of the hormone in doses of 5 or 50 micrograms/100 g body wt per 24 h, respectively, from osmotic minipumps implanted subcutaneously. In adrenal-intact rats receiving the 5-microgram dose, aldosterone levels were similar to those seen in animals fed a high K diet and produced a time-dependent increase in Na-K-ATPase activity in the cortical-collecting tubule (CCT) to a level 103% higher than in controls after 7 d (2,007 +/- 178 vs. 989 +/- 72 pmol/mm per h, P less than 0.001); the enzyme activity in the proximal convoluted tubule, medullary thick ascending limb, and the inner stripe of the medullary-collecting tubule did not change significantly. The increment in CCT Na-K-ATPase was larger (142%) in animals receiving for the same period of time the 50-micrograms dose, which produced circulating aldosterone levels similar to those of sodium-deprived rats. A significant stimulation of Na-K-ATPase activity was seen in the CCT of adrenalectomized rats after 24 h of treatment with either dose of the hormone, and at 12 h only in animals receiving the 50 micrograms/100 g per 24 h regimen. To determine whether the enhanced Na-K-ATPase activity produced by aldosterone is due to synthesis of new enzyme units or to alteration in its kinetics, we examined the ouabain-binding capacity and the affinity for Na and K of the enzyme from CCT of rabbits treated with 5 micrograms/100 g body wt per 24 h aldosterone for 3 d. These experiments revealed a parallel increment on Na-K-ATPase activity and specific [3H]ouabain binding in aldosterone-treated rabbits, while the affinity of the enzyme for either sodium or potassium was unaltered. The results of this study indicate that high physiologic levels of aldosterone simulating those measured during K loading or Na deprivation lead to a segment-specific increase in Na-K-ATPase activity in the CCT. This effect was time-and dose-dependent and was due to an increase in the number of active enzyme units. The segmental specificity and time course of the increase in enzyme activity suggest that modulation of Na-K-ATPase by aldosterone plays a role in the chronic adaptation of the CCT to altered availability of sodium and potassium, and therefore in the homeostasis of these cations by the kidney.

Authors

S K Mujais, M A Chekal, W J Jones, J P Hayslett, A I Katz