title: Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention.
abstract: BACKGROUND
  Terlipressin is a vasopressin analogue used for its potent V1a effects in cirrhotic patients. Recent data suggest that terlipressin has affinity to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water clearance. Stimulation of renal V2 receptors may also affect sodium transport via the Epithelial Sodium Channel (ENaC). Furthermore, endothelial V2 receptors may indirectly affect proximal sodium handling by increasing plasma cAMP.
  
  
  METHODS
  We investigated 18 patients with cirrhosis and ascites before and after infusion of 2 mg of terlipressin. Plasma cAMP and urine AQP2 were measured and a newly developed radioimmunoassay was used to quantify ENaC in the urine.
  
  
  RESULTS
  Mean arterial blood pressure increased from 87 ± 15 to 105 ± 19 mmHg, p < 0.001 after terlipressin infusion and GFR increased from 52 ± 6 to 69 ± 9 mL/min, p < 0.01. Urine-ENaC in ng/mmol creatinine increased from 42 ± 6 to 50 ± 7 ng/mmol creatinine, p = 0.05. Urine sodium increased from 43 ± 8 to 62 ± 9 mmol/L, p < 0.01. Plasma cAMP was not affected by terlipressin, 106 (63-673) vs. 103.5 (69-774) pmol/mL, NS. The rise in ENaC excretion correlated with the rise in AQP2 excretion, r = 0.63, p < 0.01. There was a weak correlation between the change in MAP and the rise in AQP2 excretion (p < 0.05).
  
  
  CONCLUSIONS
  Increased ENaC excretion suggests increased abundance of ENaC and resultant increased distal sodium reabsorption. The V2 effects of terlipressin are insufficient to stimulate the endothelial V2 receptors since plasma cAMP is unaltered. Despite pronounced V1a and some V2 effects of terlipressin, additional effects on proximal sodium handling are therefore not likely.
authors.affiliation: Department of Gastroenterology, Hvidovre University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark. aleksander.krag@hvh.regionh.dk
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.forename: Erling B
authors.initials: EB
authors.lastname: Pedersen
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood*; D003710:Demography; D053503:Epithelial Sodium Channels / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology / Q000652:urine*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017483:Receptors, Vasopressin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000077585:Terlipressin; D014667:Vasopressins / Q000819:agonists*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D053503:Epithelial Sodium Channels; D017483:Receptors, Vasopressin; D014667:Vasopressins; D008236:Lypressin; D000077585:Terlipressin; D012964:Sodium; D000242:Cyclic AMP