Regulation of collecting tubule adenosine triphosphatases by aldosterone and potassium.

Abstract

To examine the precise role of potassium and aldosterone on acid-base composition and on collecting tubule ATPases, glucocorticoid-replete adrenalectomized rats were replaced with zero, physiological, or pharmacological doses of aldosterone and were fed varying potassium diets to produce hypokalemia, normokalemia, or hyperkalemia. Radiochemical measurement of ATPase activities showed that collecting tubule H/KATPase changed inversely with potassium and not with aldosterone whereas H-ATPase changed directly with aldosterone but not with potassium. When both enzymes changed in the same direction, alterations in acid-base composition were profound; however, when these two acidifying enzymes changed in opposite directions or when only one enzyme changed, the effect on acid-base balance was modest. Serum bicarbonate was -45 meq/liter when aldosterone was high and potassium was low, it was only 29 meq/liter when aldosterone was high but potassium was normal or when aldosterone was normal and potassium was low. Our observations may help explain the metabolic alkalosis of primary aldosteronism in which aldosterone excess and hypokalemia are combined and the metabolic acidosis of aldosterone deficiency in which hypoaldosteronism and hyperkalemia are paired. The present study also demonstrated that aldosterone plays the major role in controlling Na/K-ATPase activity in cortical collecting tubule. Hypokalemia stimulates Na/K-ATPase activity in the medullary collecting tubule; this stimulatory effect of hypokalemia supports the hypothesis that the enzyme is present on the apical membrane at this site. (J.

Mineralocorticoids Stimulate the Activity and Expression of Renal H+,K+-ATPases

“…Overall Na ϩ and K ϩ balance was not significantly different in mice from any genotype under control conditions ( Figure 7). As expected, overall Na ϩ balance in- The effect of long-term mineralocorticoid excess to change H ϩ ,K ϩ -ATPase activity and its relation to dietary K ϩ intake has previously been examined by Eiam-Ong et al 11 In contrast to the results described here, 7-day exposure to low, normal, or high aldosterone levels in rats fed diets consisting of low, normal, and high K ϩ content did not significantly affect Schering 28080 -sensitive (a gastric or HK␣ 1 -containing H The renal H ϩ ,K ϩ -ATPases have been purported to act as primarily K ϩ reabsorptive mechanisms. Because hypokalemia has been shown to substantially increase medullary HK␣ 2 expression [17][18][19] and hypokalemia was quite evident with DOCP treatment, the induction of HK␣ 2 expression in the outer and inner medulla of DOCP-treated mice could be a result of hypokalemia.…”

Increased Endothelin Activity Mediates Augmented Distal Nephron Acidification Induced by Dietary Protein

“…This suggests that the increased H ϩ -ATPase activity that is reduced by ET A/B receptor blockade is an indirect effect of ET, possibly acting through another agent. A possible scenario is that increased renal ET production induced by dietary protein increases adrenal secretion of aldosterone (21) that in turn increases distal nephron H ϩ -ATPase activity (22). Further studies will be necessary to explore this hypothesis.…”

Aldosterone Requires Vasopressin V1a Receptors on Intercalated Cells to Mediate Acid-Base Homeostasis

“…Thus, net acid excretion was not significantly different between WT and V1aR Ϫ/Ϫ mice. Stimulation of urinary acidification by the drinking of NH 4 Cl showed a decrease in the urinary pH both in WT and V1aR Ϫ/Ϫ mice, with lower urinary pH levels observed in V1aR Ϫ/Ϫ mice ( Figure 1). The increase in net acid excretion was significantly smaller in V1aR Ϫ/Ϫ mice because of insufficient ammonium excretion.…”

“…Aldosterone and vasopressin regulates the acidbase balance by proton secretion through reabsorption of bicarbonate and the excretion of ammonium and titratable acid mainly in the collecting ducts. [1][2][3][4] Principal and intercalated cells are present in the collecting ducts. 1,2 Vasopressin regulates sodium and water transport via the V2 receptor (V2R) in the basolateral membrane of the principal cells and subsequent activation of aquaporin 2 and amiloride-sensitive epithelial sodium channel (ENaC), which is also regulated by aldosterone.…”

“…[1][2][3][4] Principal and intercalated cells are present in the collecting ducts. 1,2 Vasopressin regulates sodium and water transport via the V2 receptor (V2R) in the basolateral membrane of the principal cells and subsequent activation of aquaporin 2 and amiloride-sensitive epithelial sodium channel (ENaC), which is also regulated by aldosterone.…”