AJP - Renal Physiology, Vol 262, Issue 6 972-F979, Copyright © 1992 by American Physiological Society
Discordant aspects of aldosterone resistance in potassium depletion
S. K. Mujais, Y. Chen and N. A. Nora
Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
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.
