Renal and haemodynamic responses to a novel kappa opioid receptor agonist, niravoline (RU 51,599), in rats with cirrhosis.
Because renal water retention is a complication of cirrhosis, niravoline (RU 51,599), a novel kappa (kappa) opioid receptor agonist which is known to cause a water diuresis under normal conditions, may be useful in the therapy of chronic liver diseases. Thus, the present study examined the effects of niravoline on renal function in rats with cirrhosis. Urine was collected during the 2 h period following the administration of vehicle (saline) in one groups of animals or niravoline (3 mg/kg, i.v.) in another group. Urinary and plasma osmolality were measured prior to and 2 h after niravoline in a third group of animals. Urine flow and natraemia were significantly higher after niravoline (147 +/- 12 microL/min and 153 +/- 2 mmol/L, respectively) than after vehicle (27 +/- 7 microL/min and 146 +/- 1 mmol/L, respectively). Niravoline significantly decreased urinary osmolality and significantly increased plasma osmolality and free water clearance. This substance did not significantly change urinary sodium excretion. In conclusion, this study shows that niravoline, a kappa opioid receptor agonist, induced a water diuresis in rats with cirrhosis.
Laboratoire d'Hémodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique, INSERM U-24, Hôpital Beaujon, Clichy, France.
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Moreau
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Cailmail
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Hamon
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Lebrec
D000818:Animals; D044482:Benzeneacetamides; D004231:Diuresis / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C100946:niravoline