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

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

Is There a Role for PGE2 in Urinary Concentration?

“…94 Urinary AQP2 is a commonly used assessment of AQP2 membrane targeting because it has been shown to reflect the physiologic response to VP in the CD. 95 This suggests that prostanoid-induced AQP2 membrane targeting is also observed in humans, which increases the clinical relevance of these findings.…”

Nonsteroidal Anti-Inflammatory Drugs Alter the Human Mesothelial Pleural Permeability via Ion Cellular Transportation by Inhibiting Prostaglandin Synthesis

“…NSAIDs have been implicated in altering the endothelial permeability and the cellular transportation via ion channels in various tissues [12] such as the kidneys, where urinary sodium excretion was decreased and sodium absorption was increased by ibuprofen [1]. Indomethacin decreased the permeability increase induced by lung adenocarcinoma cells [2].…”

“…These selective inhibitors were considered to offer a better inflammatory pleural response in pleurodesis [17], thereby overcoming the decreased quality of pleural adhesions during pleurodesis induced by the nonselective NSAIDs [1,6,18]. Celecoxib, on the other hand, is considered to inhibit Na + channels in dorsal root ganglion neurons [14] or in rat retinal neurons [15].…”

“…The nonsteroidal anti-inflammatory drugs (NSAIDs), apart from anti-inflammatory and analgesic properties, have been implicated in causing permeability alterations in various tissues such as the kidneys and lungs, interfering with ion transportation across epithelial tissues [1,2]. In most cases these alterations are being mediated via interference with prostaglandin production [1,2,3].…”

“…In most cases these alterations are being mediated via interference with prostaglandin production [1,2,3]. …”