Regulation of Acid-Base Transporters by Vasopressin in the Kidney Collecting Duct of Brattleboro Rat

Abstract

Aim: The objective of these studies was to examine the effects of long-term vasopressin treatment on acid-base transporters in the collecting duct of rat kidney. Methods: Brattleboro rats were placed in metabolic cages and treated with daily injections of 1-desamino-8- D-arginine vasopressin (dDAVP), a selective V₂-receptor agonist, or its vehicle (control) for up to 8 days. Results: dDAVP treatment resulted in a significant reduction in serum bicarbonate concentration, and caused the upregulation of key ammoniagenesis enzymes, along with increased urinary NH₄⁺ excretion. Northern hybridization and immunofluorescence labeling indicated a significant increase (+80%) in mRNA expression of the apical Cl^–/HCO₃^– exchanger pendrin (PDS), along with a sharp increase in its protein abundance in B-type intercalated cells in the cortical collecting duct in dDAVP-treated rats. In the inner medullary collecting duct, the abundance of basolateral Cl^–/HCO₃^– exchanger (AE1) and apical H⁺-ATPase was significantly reduced in dDAVP-treated rats. Kidney renin mRNA increased significantly and correlated with an increase in serum aldosterone levels in dDAVP-injected rats. Serum corticosterone levels were, however, reduced and correlated with increased mRNA levels of renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and decreased mRNA expression of 11β-hydroxylase in the adrenal gland of dDAVP-injected rats. Conclusion: Chronic administration of dDAVP to Brattleboro rats is associated with the upregulation of PDS and downregulation of H⁺-ATPase and AE1 in the collecting duct, along with increased ammoniagenesis. Stimulation of the renin-angiotensin-aldosterone system and/or decreased glucocorticoid levels likely plays a role in the transduction of these effects.