H+ transport by the aldosterone-deficient rat distal nephron

Abstract

The effect of aldosterone on distal nephron acidification was investigated by comparing isolated perfused kidneys from adrenalectomized rats treated for 3 to 5 days with dexamethasone alone (10 micrograms/day i.p.) and from rats given in addition a physiologic dose of d-aldosterone (10 micrograms/day in oil s.c.). The maximal pH gradient between urine and perfusate, determined at a perfusate pH of 6.7 with glucose as the sole substrate, did not differ significantly between the aldosterone deplete and replete groups (1.27 +/- 0.12 vs. 1.35 +/- 0.12). H+ secretory capacity of the distal nephron was determined by perfusing kidneys at pH 6.8 and providing saturating quantities of urinary buffer in the form of creatinine. Under these experimental conditions kidneys from aldosterone deplete rats had a higher urine pH and lower excretion rate of titratable acid indicative of a defect in H+ secretion. Acid secretion below a pH of 6.0 (T.A.-pH 6.0), an index of H+ secretion by the distal nephron, was also significantly lower in the aldosterone deplete kidneys. Thus, aldosterone depletion decreased the H+ secretory capacity of the distal nephron, but had no clear effect on the force of the pump as reflected by the maximal pH gradient. Amiloride (10(-5) M) was added to the perfusate of kidneys undergoing the H+ secretory capacity protocol to distinguish between sodium-linked and sodium-independent effects of aldosterone. The difference in T.A. pH 6.0 between aldosterone deplete and replete kidneys was reduced by approximately 70% in the presence of amiloride. This indicates that a substantial portion of the aldosterone-dependent component of distal nephron H+ secretion is mediated by a sodium-dependent mechanism.

The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase

“…9,26,33 Consistent with these functional classifications, application of amiloride to patients and experimental animals reduces urinary proton secretion. 9,32,34 LiCl has been used as another tool to induce the voltage-dependent defect; however, several studies have indicated that the defects induced by LiCl and amiloride are different. 35 The defect induced by administration of LiCl can be restored by Na 2 SO 4 infusion 32 and is associated with altered expression levels of H þ /K þ -ATPases and H þ -ATPases.…”

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…Furthermore, aldosterone increases the activity of vacuolar H ϩ -ATPases in rat and rabbit cortical and medullary collecting ducts, and these effects are mimicked in isolated turtle bladder (32). Evidence that this mineralocorticoid is necessary for appropriate urinary acidification is also derived from patients with inborn or acquired aldosterone deficiency syndromes (distal renal tubular acidosis type IV) or in animal models with adrenalectomy or pharmacological blockade of the aldosterone pathway (10,(33)(34)(35)(36). In general, it is accepted that sustained effects of mineralocorticoids on acid secretion involve genomic mechanisms.…”