Down-regulation of urinary AQP2 and unaffected response to hypertonic saline after 24 hours of fasting in humans.
BACKGROUND
In rats, 24 hours of fasting impairs urinary concentrating ability by down-regulation of aquaporin-2 (AQP2). We tested the hypothesis that 24 hours of fasting in humans reduces the capability to form AQP2 and impairs the antidiuretic response to hypertonic saline infusion.


METHODS
In a crossover study of 14 healthy subjects, the effect of 24 hours of fasting was compared to a nonfasting control experiment on urinary excretion of AQP2 (u-AQP2), free water clearance (C(H(2)O)), plasma arginine vasopressin (AVP), urinary cyclic AMP (u-cAMP), and natriuretic peptides. The following response to 3% sodium infusion was measured using the same effect variables. U-AQP2, AVP, and u-cAMP were determined by radioimmunoassays.


RESULTS
Fasting during 24 hours reduced u-AQP2 (14%), increased AVP (30%) despite a reduction in serum osmolality (P < 0.05), and depleted volume. C(H(2)O) and urine volume were not reduced, thus relatively increased after fasting. u-cAMP was not significantly different between the two procedures. Three percent saline resulted in the same relative increases in AVP, serum osmolality, u-AQP2, and u-cAMP and decreases in C(H(2)O) and urine volume independently of fasting. The reduced u-AQP2 and increased AVP after fasting were maintained during and after saline infusion.


CONCLUSIONS
Twenty-four hours of fasting decreased u-AQP2 and reduced urine osmolality likely as a result of decreased sensitivity of collecting duct cells to AVP. Fasting-related insensitivity of collecting duct cells to AVP was restored by 3% saline infusion. Finally, after saline infusion, other factors such as the increased plasma atrial natriuretic peptide (p-ANP) levels could contribute to the u-AQP2 regulation.
Starklint
Jørn
J
Department of Medical Research, Holstebro Hospital, Holstebro, Denmark. ajos@ringamt.dk
Bech
Jesper Nørgaard
JN
Pedersen
Erling Bjerregaard
EB
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D051399:Aquaporin 2; D020346:Aquaporins / Q000652:urine*; D009320:Atrial Natriuretic Factor / Q000097:blood; D018592:Cross-Over Studies; D015536:Down-Regulation; D005215:Fasting / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012083:Renin / Q000097:blood; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
C496023:AQP2 protein, human; D051399:Aquaporin 2; D020346:Aquaporins; D012462:Saline Solution, Hypertonic; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin