title: Aquaretic effect of the kappa-opioid agonist RU 51599 in cirrhotic rats with ascites and water retention.
abstract: OBJECTIVE
  It has recently been described that kappa-opioid receptor agonists inhibit antidiuretic hormone secretion and promote water excretion in humans and experimental animals. The aim of this study was to evaluate the aquaretic efficacy of the kappa-opioid receptor agonist RU 51599 in conscious cirrhotic rats with ascites and water retention.
  
  
  METHODS
  In protocol 1, arterial pressure, heart rate, and renal water metabolism were measured in basal conditions and then were measured for 120 minutes after the administration of Ringer's solution (n = 8; 0.4 mL) or RU 51599 (n = 7; 1 mg/kg). In protocol 2, plasma antidiuretic hormone concentration was measured (n = 6) before and 60 minutes after administration of RU 51599 (1 mg/kg). In protocol 3, the effect of RU 51599 (n = 9; 1 mg/kg) was compared with that of the V2-receptor antagonist SKF 100398 (n = 9; 30 micrograms/kg).
  
  
  RESULTS
  RU 51599 administration induced a profound diuretic and aquaretic effect without altering arterial pressure and heart rate. In protocol 2, the kappa-opioid agonist reduced by about 50% plasma antidiuretic hormone levels (from 6.6 +/- 0.9 to 3.4 +/- 0.6 pg/mL; P < 0.05). Finally, the improvement in renal water metabolism induced by RU 51599 was similar to that produced by the V2-receptor antagonist.
  
  
  CONCLUSIONS
  RU 51599 has a potent aquaretic effect in cirrhotic rats with water retention, suggesting that kappa-opioid receptor agonists may be useful for the treatment of water retention and dilutional hyponatremia in cirrhosis.
authors.affiliation: Department of Medicine, Hospital Clinic i Provincial, University of Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bosch-Marcé
authors.forename: W
authors.initials: W
authors.lastname: Jiménez
authors.forename: P
authors.initials: P
authors.lastname: Angeli
authors.forename: A
authors.initials: A
authors.lastname: Leivas
authors.forename: J
authors.initials: J
authors.lastname: Clària
authors.forename: A
authors.initials: A
authors.lastname: Graziotto
authors.forename: V
authors.initials: V
authors.lastname: Arroyo
authors.forename: F
authors.initials: F
authors.lastname: Rivera
authors.forename: J
authors.initials: J
authors.lastname: Rodés
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001201:Ascites; D044482:Benzeneacetamides; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D004231:Diuresis / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011759:Pyrrolidines; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D014667:Vasopressins; D001127:Arginine Vasopressin; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin; C100946:niravoline