Urinary excretion of aquaporin-2 after furosemide and felodipine in healthy humans.
OBJECTIVE: Furosemide inhibits renal sodium and chloride reabsorption in the loop of Henle. A compensatory increased reabsorption of sodium and water takes place in the collecting duct. It is not known whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. In animals, dihydropyridine derivatives of calcium channel blockers down-regulate AQP2 in the collecting duct, but the effect has not been studied in humans. We sought to test the hypotheses that urinary excretion of aquaporin-2 (U-AQP2) increases after a single intravenous dose of furosemide, and that U-AQP2 decreases after a single oral dose of felodipine. MATERIAL AND METHODS: In two randomized, single-blind, placebo-controlled, cross-over studies, we measured the effect of furosemide and felodipine on U-AQP2, urine volume, free water clearance (CH2O), and fractional excretion of sodium (FENa) in 13 healthy subjects in each study. 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. Glomerular filtration rate (GFR) was measured by constant infusion technique. U-AQP2 and hormones were determined by radioimmunoassay. RESULTS: Furosemide treatment increased U-AQP2 (202%), urine volume (214%), and FENa by a factor of 11, (p < 0.001 for all), whereas CH2O and GFR were unchanged. After treatment with placebo, no differences were seen. Furosemide treatment increased AVP (18%), PRC (60%), ang II (100%), and aldo (98%) (p < 0.032); ANP was decreased by 29% (p < 0.001), whereas there was no change in BNP. The hormones were unchanged after placebo except for a minor decrease in ANP after placebo. Felodipine tended to increase U-AQP2, to decrease CH2O and urine volume and GFR, and to increase FENa, but the effect was not significantly different from placebo. Felodipine increased PRC (82%) (p < 0.003) and ang II, but decreased aldo, and increased AVP. After placebo, PRC was unchanged, whereas ang II, aldo and AVP were changed as after felodipine. CONCLUSIONS: Furosemide treatment increased U-AQP2, AVP, and the activity of the renin-angiotensin-aldosterone system. These changes are most likely compensatory phenomena, which prevent an excess loss of sodium and water. Felodipine tended to increase U-AQP2.[1]References
- Urinary excretion of aquaporin-2 after furosemide and felodipine in healthy humans. Starklint, J., Bech, J.N., Pedersen, E.B. Scand. J. Clin. Lab. Invest. (2005) [Pubmed]
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