Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites

J Hepatol. 1997 Jun;26(6):1229-34. doi: 10.1016/s0168-8278(97)80456-4.


Background/aims: Refractory ascites, which occurs in certain patients with cirrhosis, is associated with a blunted natriuretic response to exogenous atrial natriuretic peptide (ANP). Since this blunting seems to be related to ANP-induced arterial hypotension, a vasoconstrictor, such as terlipressin (a vasopressin analogue), may restore natriuresis to exogenous ANP. Moreover, since cirrhosis-elicited vasodilation is thought to play a role in sodium retention, a vasoconstriction caused by terlipressin alone may lead to an increase in sodium excretion. This study aimed to evaluate the natriuretic response to either a combination of ANP with terlipressin or terlipressin alone in patients with cirrhosis and refractory ascites.

Methods: Sixteen consecutive patients with cirrhosis and refractory ascites were randomly assigned to receive either a combination of terlipressin (1-2 mg, i.v. bolus) with ANP (35 ng/kg, i.v. bolus followed by 15 ng x kg(-1) x min(-1) for 60 min) (n=8) or terlipressin alone (1-2 mg, i.v. bolus) (n=8). Sodium excretion and urine output, systemic, splanchnic and renal hemodynamics and renal oxygen consumption were measured before and during treatments.

Results: Combined therapy did not change arterial pressure but significantly increased urinary sodium excretion and urine output. These effects were associated with a significant increase in glomerular filtration rate and a decrease in renal oxygen consumption. Terlipressin alone significantly increased arterial pressure but did not change urinary sodium excretion or urine output. Moreover, terlipressin did not change either glomerular filtration rate or renal oxygen consumption.

Conclusions: The combination of exogenous ANP with terlipressin, but not terlipressin alone, increases sodium excretion in patients with cirrhosis and refractory ascites.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use*
  • Ascites / drug therapy*
  • Ascites / physiopathology
  • Atrial Natriuretic Factor / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Kidney / blood supply
  • Liver Cirrhosis, Alcoholic / drug therapy*
  • Liver Cirrhosis, Alcoholic / physiopathology
  • Lypressin / analogs & derivatives*
  • Lypressin / therapeutic use
  • Male
  • Natriuresis* / drug effects
  • Regional Blood Flow / drug effects
  • Renal Circulation / drug effects
  • Renal Circulation / physiology*
  • Splanchnic Circulation / drug effects
  • Splanchnic Circulation / physiology*
  • Terlipressin
  • p-Aminohippuric Acid / pharmacokinetics


  • Antihypertensive Agents
  • Lypressin
  • Terlipressin
  • Atrial Natriuretic Factor
  • p-Aminohippuric Acid