Discordant aspects of aldosterone resistance in potassium depletion.
Aldosterone resistance, defined as absent kaliuretic response to exogenous hormone, has been described in K depletion. It is not clear whether the absent kaliuresis is due to activation of K-conserving mechanisms or to failure of activation of the Na-K pump in cortical collecting tubules (CCT) by mineralocorticoids. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal or low-K diet. Na-K pump activity (pmol.mm-1.h-1) in microdissected CCT and medullary collecting tubules (MCT, inner stripe of the outer medulla) was determined at 7 or 21 days after allocation to the dietary groups before and after exogenous aldosterone (50 micrograms twice daily, for 3 days). K depletion led to progressive hypertrophic changes in the CCT and MCT manifest in an increase in basal Na-K pump activity. In both K repletion and short-term K depletion (7 days), aldosterone led to the expected increase in CCT Na-K pump activity. With long-term K depletion, the CCT Na-K pump response to aldosterone was blunted. In the MCT where under normal conditions the Na-K pump is aldosterone unresponsive, an increasing aberrant responsiveness to the mineralocorticoid was observed with progressive K depletion. We conclude that apparent aldosterone resistance in short-term K depletion is likely due to activation of K-conserving mechanisms with early preservation of the CCT biochemical response to the hormone. With long-term K depletion, a blunted biochemical response to aldosterone may contribute to the absent kaliuretic response. In the MCT, K depletion led to the development of aberrant responsiveness to aldosterone.
Mujais
S K
SK
Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
Chen
Y
Y
Nora
N A
NA
D000251:Adenosine Triphosphatases / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D004351:Drug Resistance; D007685:Kidney Tubules, Collecting / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D011191:Potassium Deficiency / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase
D000450:Aldosterone; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase