Increased urinary aquaporin-2 excretion in response to furosemide in patients with chronic heart failure.
OBJECTIVE
Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U-AQP2 increases after a single intravenous dose of furosemide in CHF patients.


METHODS
In a randomized, single-blind, placebo-controlled, crossover study, we measured the effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U-AQP2 and hormones were determined by radioimmunoassays.


RESULTS
Furosemide increased U-AQP2 (140 %), urine volume (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change.


CONCLUSIONS
In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin-angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.
Starklint
J
J
Department of Medical Research, Holstebro Hospital, DK-7500 Holstebro, Demark. j.starklint@dadlnet.dk
Bech
J N
JN
Nyvad
O
O
Jensen
P
P
Pedersen
E B
EB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000097:blood; D051399:Aquaporin 2 / Q000652:urine*; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D005260:Female; D005665:Furosemide / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012083:Renin / Q000097:blood
C496023:AQP2 protein, human; D051399:Aquaporin 2; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D005665:Furosemide; D009320:Atrial Natriuretic Factor; D012083:Renin