Biphasic effects of ANP infusion in conscious, euvolumic rats: roles of AQP2 and ENaC trafficking.
Atrial natriuretic peptide (ANP) acutely promotes water and sodium excretion, whereas subchronic effects involve water retention. Renal hemodynamics, water and sodium excretion, and aquaporin-2 (AQP2) and epithelial Na channel (ENaC) subcellular trafficking were determined in response to continuous ANP infusion in conscious rats, where body sodium and fluid balance was constantly maintained. ANP (0.5 microg x kg(-1) x min(-1)) evoked a transient (peak at 10 min) fivefold diuresis followed by reduced urine production to control levels (30- to 90-min period). The fractional distal water excretion was significantly increased initially and then decreased in response to ANP. There was no change in the subcellular localization of AQP2 and AQP2 phosphorylated in PKA consensus site S256 (p-AQP2) 10 min after ANP infusion. In contrast, after 90 min a marked increase in apical labeling of AQP2 and p-AQP2 was observed in the inner and outer medullary collecting ducts but not in cortical collecting ducts. In support of this, ANP induced plasma membrane targeting of AQP2 in transiently AQP2-transfected cells. ANP infusion evoked an instant increase in renal sodium excretion, which persisted for 90 min. Ten minutes of ANP infusion induced no changes in the subcellular localization of ENaC subunits, whereas a marked increase in apical targeting of alpha- and gamma-subunits was observed after 90 min. In conclusion, 1) ANP infusion induced a sustained natriuresis and transient diuresis; 2) there were no changes in the subcellular localization of AQP2 and ENaC subunits after 10 min of ANP infusion; and 3) there was a marked increase in apical targeting of AQP2, p-AQP2, and alpha- and gamma-ENaC after 90 min of ANP infusion. The increased targeting of ENaC and AQP2 likely represents direct or compensatory effects to increase sodium and water reabsorption and to prevent volume depletion in response to prolonged ANP infusion.
Wang
Weidong
W
The Water and Salt Research Center, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark.
Li
Chunling
C
Nejsum
Lene N
LN
Li
Hongyan
H
Kim
Soo Wan
SW
Kwon
Tae-Hwan
TH
Jonassen
Thomas E N
TE
Knepper
Mark A
MA
Thomsen
Klaus
K
Frøkiaer
Jørgen
J
Nielsen
Søren
S
D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002460:Cell Line; D053503:Epithelial Sodium Channels; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism / Q000652:urine; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014554:Urination / Q000187:drug effects; D014882:Water-Electrolyte Balance
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D009320:Atrial Natriuretic Factor; D012964:Sodium