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1The Water and Salt Research Center, University of Aarhus, and 2Institute of Clinical Medicine, Aarhus University Hospital-Skejby, Aarhus; 3Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; 4Department of Pharmacology, University of Copenhagen, Copenhagen; 5Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and 6Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Aarhus University Hospital, Aarhus, Denmark
Submitted 17 February 2005 ; accepted in final form 15 September 2005
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 µg·kg1·min1) 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
- and
-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
- and
-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.
aquaporin-2; atrial natriuretic peptide; cGMP; collecting duct; diuresis; epithelial sodium channel; natriuresis; servo-controlled replacement
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