Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney.
The purpose of the present studies was to determine the effects of high-dose aldosterone and dDAVP treatment on renal aquaporin-2 (AQP2) regulation and urinary concentration. Rats were treated for 6 days with either vehicle (CON; n = 8), dDAVP (0.5 ng/h, dDAVP, n = 10), aldosterone (Aldo, 150 microg/day, n = 10) or combined dDAVP and aldosterone treatment (dDAVP+Aldo, n = 10) and had free access to water with a fixed food intake. Aldosterone treatment induced hypokalemia, decreased urine osmolality, and increased the urine volume and water intake in ALDO compared with CON and dDAVP+Aldo compared with dDAVP. Immunohistochemistry and semiquantitative laser confocal microscopy revealed a distinct increase in basolateral domain AQP2 labeling in cortical collecting duct (CCD) principal cells and a reduction in apical domain labeling in Aldo compared with CON rats. Given the presence of hypokalemia in aldosterone-treated rats, we studied dietary-induced hypokalemia in rats, which also reduced apical AQP2 expression in the CCD but did not induce any increase in basolateral AQP2 expression in the CCD as observed with aldosterone treatment. The aldosterone-induced basolateral AQP2 expression in the CCD was thus independent of hypokalemia but was dependent on the presence of sodium and aldosterone. This redistribution was clearly blocked by mineralocorticoid receptor blockade. The increased basolateral expression of AQP2 induced by aldosterone may play a significant role in water metabolism in conditions with increased sodium reabsorption in the CCD.
de Seigneux
Sophie
S
The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark.
Nielsen
Jakob
J
Olesen
Emma T B
ET
Dimke
Henrik
H
Kwon
Tae-Hwan
TH
Frøkiaer
Jørgen
J
Nielsen
Søren
S
D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D007008:Hypokalemia / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D010766:Phosphorylation; D011191:Potassium Deficiency / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012076:Renal Agents / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014867:Water / Q000378:metabolism
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D012076:Renal Agents; D014867:Water; D000804:Angiotensin II; D012694:Serine; D000450:Aldosterone; D003894:Deamino Arginine Vasopressin