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

Disclosures

BMC Nephrology. 2010;11 

In This Article

Background

Inhibition of prostaglandin synthesis reduces renal water and sodium excretion in the kidneys, especially in patients with renal disease or heart failure. A recent study suggested that increased absorption of sodium took place in the thick ascending limb of Henle during prostaglandin inhibition.[1] However, the distal part of the nephron might also participate in this process, i. e. by an increase in the absorption of water and sodium via the aquaporine2 water channels (AQP2) and epithelial sodium channels (ENaC), respectively. The effect of prostaglandin inhibition on renal water and sodium excretion is most pronounced during conditions with an increased prostaglandin synthesis. During fasting, urinary concentrating and diluting ability was reduced, and AQP2 expression down regulated, possibly due to an antagonizing effect of increased prostaglandin level on the effect of vasopressin on water transport in the principal cells.[2–5] In addition, fasting induced natriuresis in man, and prostaglandin E2 inhibited sodium absorption in the collecting ducts in rats and rabbits.[6–8] Thus, elevated renal levels of prostaglandin during fasting might mediate natriuresis via ENaC.[9] The degree of water transport via AQP2 is reflected by the level of urinary excretion of aquaporine2 (u-AQP2).[10] Correspondingly, the sodium transport via ENaC is supposed to be reflected by level of urinary excretion of the β-fraction of ENaC (u-ENaCβ). This is the first report with measurement of u-ENaCβ as a biomarker of the activity of the epithelial sodium channels in the distal tubuli.

In the present study, we measured the effect of inhibition of prostaglandins on u-AQP2 and u-ENaCβ during fasting. We wanted to test the hypotheses that a reduction of prostaglandin synthesis by ibuprofen treatment during fasting would 1. Increase u-AQP2 and u-ENaCβ during baseline condition and change the renal response to hypertonic saline infusion, and 2. The increased renal water and sodium absorption during ibuprofen treatment was mediated via increased transport via AQP2 and ENaC.

We performed a randomized, placebo controlled crossover study in healthy humans during baseline condition and during hypertonic saline infusion to examine the effect of ibuprofen on renal handling of water and sodium during fasting. We measured the effect of ibuprofen/placebo on u-AQP2, u-ENaCβ, fractional urinary excretion of sodium (FENa), urinary excretion of prostaglandin E2 (u-PGE2), urinary excretion of cyclic AMP (u-c-AMP), free water clearance (CH2O), and plasma concentrations of renin (PRC), angiotensin II (p-Ang II), aldosterone (p-Aldo), vasopressin (p-AVP), atrial natriuretic peptide (p-ANP), and brain natriuretic peptide (p-BNP).

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