Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

Thomas G Lauridsen, Henrik Vase, Jørn Starklint, Carolina C Graffe, Jesper N Bech, Søren Nielsen, Erling B Pedersen, Thomas G Lauridsen, Henrik Vase, Jørn Starklint, Carolina C Graffe, Jesper N Bech, Søren Nielsen, Erling B Pedersen

Abstract

Background: 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 aquaporin2 water channels and the epithelial sodium channels.

Methods: The 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.

Results: Ibuprofen 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.

Conclusion: During 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 system

Trial registration: Clinical Trials Identifier: NCT00281762.

Figures

Figure 1
Figure 1
Effect hypertonic saline infusion on ENaCb/crea in a randomized placebo-controlled, cross-over study of 17 healthy subjects.
Figure 2
Figure 2
Effect hypertonic saline infusion on fractional sodium excretion (FENa) in a randomized placebo-controlled, cross-over study of 17 healthy subjects.

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