Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects

• Published in: American journal of physiology. Renal physiology Vol. 295; no. 5; pp. F1295 - F1300
• Main Authors: Krag, Aleksander, Bendtsen, Flemming, Pedersen, Erling Bjerregaard, Holstein-Rathlou, Niels-Henrik, Møller, Søren
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2008
• Subjects: Adolescent; Adult; Aged; Antidiuretic Agents - pharmacology; Aquaporin 2 - urine; Arginine Vasopressin - blood; Blood Pressure - drug effects; Blood Pressure - physiology; Creatinine - urine; Cyclic AMP - urine; Drinking - drug effects; Drinking - physiology; Drugs; Female; Hepatorenal Syndrome - drug therapy; Hepatorenal Syndrome - metabolism; Hormones; Humans; Kidney - drug effects; Kidney - physiology; Lithium - urine; Lypressin - analogs & derivatives; Lypressin - pharmacology; Lypressin - therapeutic use; Male; Middle Aged; Osmolar Concentration; Receptors, Vasopressin - agonists; Sodium - blood; Studies; T cell receptors; Urine; Urine - chemistry; Vasoconstrictor Agents - pharmacology; Water - metabolism; Water-Electrolyte Balance - drug effects; Water-Electrolyte Balance - physiology; Young Adult
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.90407.2008

The vasopressin analog terlipressin is believed to cause vasoconstriction selectively by V 1 receptor stimulation. However, a possible antidiuretic effect by V 2 receptor stimulation has never been ruled out. Twenty-two patients with ascites, including seven with refractory ascites, were included. The subjects were studied during a 400 ml/h oral water load before and after infusion of 2 mg of terlipressin (18 patients) or placebo infusion (4 patients). Effects on the V 2 receptors were assessed by evaluating aquaporin (AQP)2 excretion, free water clearance (C[Formula: see text]), urine osmolality (U osm ), and fractional distal water excretion (DFeH 2 O). After terlipressin the excretion of AQP2 increased by 89% [144 ng/mmol creatinine, 95% confidence interval (CI) 73–214 ng/mmol creatinine, P = 0.001]. C[Formula: see text] decreased 1.05 ml/min (from 0.17 to −0.89 ml/min, P = 0.001), and DFeH 2 O decreased 37% (19 vs. 12; 95% CI 2–11, P = 0.01). U osm increased by 27% (93 mosmol/kgH 2 O, 95% CI 23–164 mosmol/kgH 2 O, P = 0.02). Plasma sodium decreased 1.1 mmol/l ( P < 0.01). An increase in AQP2 excretion and a decrease in C[Formula: see text] and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V 2 receptor effect).