Arginine vasopressin-dependent and AVP-independent mechanisms of renal fluid absorption during thirsting despite glucocorticoid-mediated vasopressin suppression

Authors

  • Friederike Ufer,

    1. Medical Clinic of Endocrinology, Diabetes and Nutrition, Charite – Universitätsmedizin Berlin, Berlin, Germany
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  • Sven Diederich,

    1. Endokrinologikum, Berlin, Germany
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  • Erling B. Pedersen,

    1. Department of Medical Research, Holstebro Hospital, Aarhus University, Aarhus, Denmark
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  • Joachim Spranger,

    1. Medical Clinic of Endocrinology, Diabetes and Nutrition, Charite – Universitätsmedizin Berlin, Berlin, Germany
    2. Experimental and Clinical Research Center (ECRC), Charite – Universitätsmedizin Berlin and Max-Delbrück Centre, Berlin, Germany
    3. Charité Center for Cardiovascular Research (CCR), Charite – Universitätsmedizin Berlin, Berlin
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  • Andreas F. H. Pfeiffer,

    1. Medical Clinic of Endocrinology, Diabetes and Nutrition, Charite – Universitätsmedizin Berlin, Berlin, Germany
    2. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
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  • Volker Bähr,

    1. Medical Clinic of Endocrinology, Diabetes and Nutrition, Charite – Universitätsmedizin Berlin, Berlin, Germany
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    • These authors contributed equally to this manuscript.

  • Knut Mai

    Corresponding author
    1. Experimental and Clinical Research Center (ECRC), Charite – Universitätsmedizin Berlin and Max-Delbrück Centre, Berlin, Germany
    • Medical Clinic of Endocrinology, Diabetes and Nutrition, Charite – Universitätsmedizin Berlin, Berlin, Germany
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    • These authors contributed equally to this manuscript.


Correspondence: Knut Mai, Medical Clinic of Endocrinology, Diabetes and Nutrition, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin. Tel.: +49 30 450 514252; Fax: +49 30 450 514950; E-mail: knut.mai@charite.de

Summary

Objective

Glucocorticoids seem to modify the release and effects of plasma arginine vasopressin (pAVP). However, underlying processes are not well understood. This study aimed to evaluate the mechanism of the modulating effects of glucocorticoids on pAVP and renal water reabsorption.

Design

Fluid deprivation tests were performed without (d0) and after one (d1) and five days (d5) of oral prednisolone (Pred) pretreatment in a dosage relevant to drug therapy (30 mg/day).

Patients

Twelve healthy male volunteers participated in this trial.

Measurements

Plasma and urinary osmolality, pAVP, renin, aldosterone, plasma atrial natriuretic peptide (ANP) as well as urinary secretion of aquaporin-2 (AQP2) and prostaglandin E2 (PGE2) were analysed.

Results

An appropriate rise in pAVP was observable during thirsting (P < 0·001), which was absent after Pred pretreatment. However, the plasma and urinary osmolality after Pred treatment did not differ when compared with the basal thirsting test. Unchanged urinary AQP2 excretion suggests AVP-independent mechanisms of renal fluid reabsorption. Plasma renin concentration as well as ANP was substantially increased after Pred intake at d1 and d5 (both P < 0·05), which may mediate such AVP-independent mechanisms. Urinary PGE2 secretion was not influenced by Pred pretreatment, making a PGE2-mediated effect on renal AQP2 translocation and water permeability unlikely. Increased efficacy of exogenous desmopressin at d1 and d5 indicates also a relative increase in AVP sensitivity of the tubular cells after Pred intake.

Conclusions

The here presented data are compatible with an increased AVP sensitivity and a partially AVP-independent regulation of AQP2 translocation and renal fluid reabsorption during glucocorticoid treatment.

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