K-INFUSION CORRECTS THICK ASCENDING LIMB CL-REABSORPTION IN K-DEPLETED RATS BY AN ALDOSTERONE-INDEPENDENT MECHANISM

Others have provided evidence that thick ascending limb (TAL) NaCl reabsorption is aldosterone dependent in adrenalectomized animals. In rats fed a K-free diet, plasma K concentration ([K]) is reduced and plasma aldosterone concentration [Aldo] is decreased. Because aldosterone release is regulated by extracellular fluid (ECF) [K], the purpose of the present study was to determine whether aldosterone deficiency mediates inhibition of TAL NaCl transport in K-depleted rats (K-Dep). Cl reabsorption was measured in functionally isolated loop segments microperfused in vivo (22 nl/min) using a modified perfusate that minimizes proximal nephron reabsorption. The results of our studies show that the defect in TAL Cl reabsorption in K-Dep rats is quantitatively significant and can be rapidly reversed by the acute systemic infusion of K. However, acute administration of aldosterone, in the presence of sustained K-Dep, failed to reverse the impairment in TAL Cl reabsorption in K-Dep rats. Furthermore, acute infusion of K, in the presence of an aldosterone antagonist, in K-Dep rats rapidly corrected the defect in TAL Cl reabsorption. Additional studies showed that despite normalization of ECF [K] by acute K infusion in K-Dep rats, plasma [Aldo] failed to increase. In contrast, acute infusion of KCl in control rats increased plasma [Aldo] by 46%, but Cl reabsorption was unchanged. In summary, these results provide conclusive evidence that the correction of defective TAL Cl reabsorption in response to the acute administration of K in K-Dep rats occurs via an aldosterone-independent mechanism. In addition, although aldosterone is required for normal TAL Cl transport, the results of the present study show that this steroid hormone does not regulate Cl reabsorption by this nephron segment.