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

Abstract

The vasopressin analog terlipressin is believed to cause vasoconstriction selectively by V1 receptor stimulation. However, a possible antidiuretic effect by V2 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 V2 receptors were assessed by evaluating aquaporin (AQP)2 excretion, free water clearance (C(H2O)), urine osmolality (Uosm), and fractional distal water excretion (DFeH2O). 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(H2O) decreased 1.05 ml/min (from 0.17 to -0.89 ml/min, P = 0.001), and DFeH2O decreased 37% (19 vs. 12; 95% CI 2-11, P = 0.01). Uosm increased by 27% (93 mosmol/kgH2O, 95% CI 23-164 mosmol/kgH2O, P = 0.02). Plasma sodium decreased 1.1 mmol/l (P < 0.01). An increase in AQP2 excretion and a decrease in C(H2O) and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V2 receptor effect).