Abstract
BackgroundTreatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels.MethodsThe effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide.ResultsIbuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher.ConclusionDuring inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone systemTrial RegistrationClinical Trials Identifier: NCT00281762
Highlights
Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion
We found that ibuprofen significantly reduced urinary excretion of prostaglandin E2 (u-PGE2) due to a reduced renal prostaglandin synthesis
Our study in healthy man is in agreement with these findings, in the sense that we found a reduction in urinary excretion of aquaporine2 (u-aquaporine2 water channels (AQP2)) excretion without changes in urinary excretion of cAMP
Summary
Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin water channels and the epithelial sodium channels. The degree of water transport via AQP2 is reflected by the level of urinary excretion of aquaporine (u-AQP2) [10]. The sodium transport via ENaC is supposed to be reflected by level of urinary excretion of the b-fraction of ENaC (u-ENaCb). This is the first report with measurement of u-ENaCb as a biomarker of the activity of the epithelial sodium channels in the distal tubuli
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