Aquaretic effect of the kappa-opioid agonist RU 51599 in cirrhotic rats with ascites and water retention.
Gastroenterology
; 109(1): 217-23, 1995 Jul.
Article
en En
| MEDLINE
| ID: mdl-7797019
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirrolidinas
/
Agua Corporal
/
Receptores Opioides kappa
/
Bencenoacetamidas
/
Diuresis
/
Cirrosis Hepática Experimental
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Revista:
Gastroenterology
Año:
1995
Tipo del documento:
Article
País de afiliación:
España