Potassium infusion in chronic potassium depleted rats rapidly reverses defective thick ascending limb chloride reabsorption by an aldosterone independent mechanism.
Creators: name: McKay, Andrea J.
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 1993
Subjects: subject: Biology, Animal Physiology.

description: Previous studies from our laboratory, using a modified loop microperfusion technique (microstop-flow conductivity) in vivo, have shown that NaCl transport by the thick ascending limb (TAL) is impaired in potassium depleted (K-DEP) rats. The degree of impairment in TAL NaCl transport is highly correlated with plasma potassium (K$\sp+$) concentration and is completely reversed when extracellular fluid potassium concentration (ECF (K$\sp+$)) is increased by acute potassium infusion. These experiments assessed NaCl transport by the TAL in the absence of axial flow by measuring the conductivity of tubular fluid emerging from an early distal tubule site after different intervals of stop-flow (10-60 seconds) in perfused nephrons. Since these measurements of TAL transport were made in the absence of axial flow, the significance of the defect in NaCl transport in K-DEP rats could not be determined under in vivo conditions of physiological flow and chloride (Cl$\sp-$) delivery. To determine the quantitative importance of this impairment in NaCl transport by the TAL, Cl$\sp-$ reabsorption was measured in functionally isolated perfused single loops of Henle in vivo, using the technique of continuous microperfusion. Cl$\sp-$ reabsorption was measured in loop segments microperfused at 22 nL/minute using a modified perfusate which minimized proximal nephron transport. This modification of the loop perfusate allowed the measurement of furosemide-sensitive Cl$\sp-$ reabsorption in the perfused loop segments such that net Cl$\sp-$ uptake in this study can be attributed primarily to carrier-mediated Cl$\sp-$ transport by the TAL. Others have provided evidence that TAL NaCl reabsorption is aldosterone dependent in adrenalectomized animals. In our rats given a K-free diet, both plasma (K$\sp+$) and plasma (aldosterone) were significantly reduced. Since aldosterone release is regulated by ECF (K$\sp+$), the purpose of the present study was to determine whether an aldosterone deficiency and/or reduced ECF (K$\sp+$) mediates inhibition of TAL Cl$\sp-$ transport in potassium depletion. Using the described microperfusion conditions, it was possible to show that the defect in TAL Cl$\sp-$ reabsorption in K-DEP rats was quantitatively significant and can be rapidly reversed by the acute systemic infusion of potassium. Acute administration of aldosterone, in the presence of sustained hypokalemia, failed to reverse the impairment in TAL Cl$\sp-$ reabsorption in K-DEP rats. However, the acute infusion of potassium, in the presence of an aldosterone antagonist, in K-DEP rats rapidly reversed the defect in TAL Cl$\sp-$ reabsorption to control levels. Additional studies showed that despite normalization of ECF (K$\sp+$) by acute potassium infusion in K-DEP rats, aldosterone levels failed to increase to control levels within this time period. This is the first study to demonstrate that the restoration of plasma (K$\sp+$) in K-DEP rats is not immediately associated with a parallel rise in plasma (aldosterone). As well, new knowledge was obtained from the present studies which showed that although a minimal (aldosterone) is required for normal TAL Cl$\sp-$ transport to occur, this steroid hormone does not regulate Cl$\sp-$ reabsorption by this nephron segment. Therefore, these results provide conclusive evidence that in K-DEP rats the rapid reversal of defective TAL Cl$\sp-$ reabsorption seen with acute potassium infusion occurs via an aldosterone independent mechanism.