Regulation of acid-base transporters by vasopressin in the kidney collecting duct of Brattleboro rat.
OBJECTIVE
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 11beta-hydroxysteroid dehydrogenase-2 (11beta-HSD2) and decreased mRNA expression of 11beta-hydroxylase in the adrenal gland of dDAVP-injected rats.


CONCLUSIONS
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.
Amlal
Hassane
H
Division of Nephrology and Hypertension, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0585, USA. hassane.amlal@uc.edu
Sheriff
Sulaiman
S
Faroqui
Somia
S
Ma
Liyun
L
Barone
Sharone
S
Petrovic
Snezana
S
Soleimani
Manoocher
M
D000450:Aldosterone / Q000032:analysis / Q000097:blood; D000641:Ammonia / Q000652:urine; D000818:Animals; D050034:Antidiuretic Agents / Q000097:blood / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D001806:Blood Urea Nitrogen; D027963:Chloride-Bicarbonate Antiporters / Q000096:biosynthesis* / Q000502:physiology; D003404:Creatinine / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004573:Electrolytes / Q000097:blood; D007685:Kidney Tubules, Collecting / Q000737:chemistry*; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011910:Rats, Brattleboro; D014667:Vasopressins / Q000097:blood / Q000494:pharmacology*
D050034:Antidiuretic Agents; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D004573:Electrolytes; D012333:RNA, Messenger; D014667:Vasopressins; D000450:Aldosterone; D000641:Ammonia; D003404:Creatinine; D003894:Deamino Arginine Vasopressin