Aquaretic effect of the kappa-opioid agonist RU 51599 in cirrhotic rats with ascites and water retention.

Abstract

BACKGROUND & AIMS:

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: M Bosch-Marcé, W Jiménez, P Angeli, A Leivas, J Clària, A Graziotto, V Arroyo, F Rivera, J Rodés
• Journal: Gastroenterology (Gastroenterology) Vol. 109 Issue 1 Pg. 217-23 (Jul 1995) ISSN: 0016-5085 [Print] United States
• PMID: 7797019 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzeneacetamides
• Pyrrolidines
• Receptors, Opioid, kappa
• Vasopressins
• Arginine Vasopressin
• 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin
• niravoline

Topics

• Analysis of Variance
• Animals
• Arginine Vasopressin (analogs & derivatives, pharmacology)
• Ascites
• Benzeneacetamides
• Blood Pressure (drug effects)
• Body Water (metabolism)
• Diuresis (drug effects)
• Heart Rate (drug effects)
• Kidney (drug effects, metabolism)
• Liver Cirrhosis, Experimental (metabolism, physiopathology)
• Male
• Natriuresis (drug effects)
• Pyrrolidines
• Rats
• Rats, Wistar
• Receptors, Opioid, kappa (agonists, metabolism)
• Vasopressins (antagonists & inhibitors, blood)