Catecholamines trigger proximal tubular fluid retention and reduce renal excretion of solute-free water. In advanced cirrhosis, non-osmotic hypersecretion of vasopressin (antidiuretic hormone or ADH) is considered the cause of dilutional hyponatraemia, but ADH V2 receptor antagonists are not beneficial in long-term treatment of ascites. To test the hypothesis that water retention in experimental ascitic cirrhosis might depend primarily on adrenergic hyper-function, hormonal status, renal function and tubular free-water reabsorption (TFWR) were assessed in six groups of rats with ascitic cirrhosis: rats with cirrhosis due to 13-week CCl4 (carbon tetrachloride) administration (group G1); cirrhotic rats receiving daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K+-canrenoate) from the 11th to the 13th week of CCl4 (G2), diuretics associated with guanfacine oral prodrug (α2A-adrenergic receptor agonist and sympatholytic agent) at 2 (G3), 7 (G4) or 10 (G5) mg/kg, or with SSP-004240F1 (V2 receptor antagonist) at 1 mg/kg (G6). Natriuresis was lower in G1 than in G2, G4 and G6 (all P<0.05). Guanfacine, added to diuretics (i.e. G3 compared with G2), reduced serum noradrenaline from 423±22 to 211±41 ng/l (P<0.05), plasma renin activity (PRA) from 35±8 to 9±2 ng/ml/h (P<0.05) and TFWR from 45±8 to 20±6 μl/min (P<0.01). TFWR correlated with plasma aldosterone (r=0.51, P<0.01) and urinary potassium excretion (r=0.90, P<0.001). In ascitic cirrhosis, reduced volaemia, use of diuretics (especially furosemide) and adrenergic hyper-function cause tubular retention of water. Suitable doses of sympatholytic agents are effective aquaretics.
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January 2016
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Cover Image
Representative photograph of Massons's trichrome-stained section of an epidermal wound in a mouse with streptozotocin-induced diabetes treated with a kinin B2 receptor antagonist. For further information please see pp. 45-56. Original image courtesy of D. Desposito, C. Chollet, C. Taveau, V. Descamps, F. Alhenc-Gelas, R. Roussel, N. Bouby and L. Waeckel.
Research Article|
December 09 2015
Pathogenesis of solute-free water retention in experimental ascitic cirrhosis: is vasopressin the only culprit?
Giovanni Sansoè;
*Division of Gastroenterology, Gradenigo Hospital, 10135 Torino, Italy
Correspondence: Dr Giovanni Sansoè, Division of Gastroenterology, Gradenigo Hospital, Corso Regina Margherita 10, 10153 Torino, Italy (email giovannisan@iol.it).
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Manuela Aragno;
Manuela Aragno
†Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy
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Raffaella Mastrocola;
Raffaella Mastrocola
†Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy
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Maurizio Parola
Maurizio Parola
†Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy
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Publisher: Portland Press Ltd
Received:
July 08 2015
Revision Received:
October 06 2015
Accepted:
October 30 2015
Accepted Manuscript online:
October 30 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (2): 117–124.
Article history
Received:
July 08 2015
Revision Received:
October 06 2015
Accepted:
October 30 2015
Accepted Manuscript online:
October 30 2015
Citation
Giovanni Sansoè, Manuela Aragno, Raffaella Mastrocola, Maurizio Parola; Pathogenesis of solute-free water retention in experimental ascitic cirrhosis: is vasopressin the only culprit?. Clin Sci (Lond) 1 January 2016; 130 (2): 117–124. doi: https://doi.org/10.1042/CS20150479
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