Effect of an acute oral ibuprofen intake on urinary aquaporin-2 excretion in healthy humans.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase and thereby block the prostaglandin (PG) synthesis in the kidneys. In animals, PG interferes with the formation of aquaporin 2 in the distal renal tubules. The purpose was to measure the effect of ibuprofen on urinary excretion of aquaporin-2 (u-AQP2), urinary output, urinary osmolality (u-osm) and plasma concentration of vasopressin (AVP) in a dose-response study using placebo and ibuprofen 600mg and 1200mg. In 12 healthy subjects, urine was collected in 6 periods between 07.00 h and 13.00 h, and blood samples were drawn at 60-min intervals. The study medication was given 10 h and 1 h before the study. U-AQP2 and AVP were determined by radioimmunoassays. U-AQP2 decreased 33% in the placebo group and increased 47% in the ibuprofen groups. There was a highly significant difference between the placebo group, on the one hand, and the ibuprofen groups, on the other. There was a small but significant increase in AVP in the placebo group and the 600 mg ibuprofen group, but not in the 1200 mg ibuprofen group. Urinary output was at maximum after 2 h, with a 394%, 1020% and 714% increase for placebo, 600 mg ibuprofen and 1200 mg ibuprofen, respectively. U-osm decreased during the experiment in all three groups. Inhibition of renal prostaglandin synthesis by ibuprofen affects the distal part of the nephron by increasing u-AQP2. This increase was not related to changes in AVP, urinary output or urinary osmolality. We suggest that the increased excretion of AQP2 can be explained by an increase in the ratio of AQP2 that is shed into the urine because the endocytic retrieval of AQP2 from the apical membrane is impaired. This could not be revealed by changes in the osmoregulatory system by the low doses of ibuprofen used in the present study.
Pedersen
R S
RS
Department of Medicine, Holstebro Hospital, Denmark. arsp@ringamt.dk
Bentzen
H
H
Bech
J N
JN
Pedersen
E B
EB
D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000652:urine*; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D012016:Reference Values; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D014556:Urine; D014867:Water / Q000378:metabolism
C496023:AQP2 protein, human; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D014867:Water; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D007052:Ibuprofen