Abstract
κ-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention.
Footnotes
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Send reprint requests to: Dr. Wladimiro Jiménez, Laboratorio Hormonal, Hospital Clinic Universitari, Villarroel 170, Barcelona 08036, Spain. E-mail: wjimenez{at}medicina.ub.es
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↵1 This work was supported in part by grants from Plan Nacional de I+D, Comisión Interministerial de Ciencia y Tecnologı́a (SAF96-0082 and SAF96-0131), and Roussel Uclaf Laboratories. M.B.-M. and M.M.-R. received a grant from FundacióPrivada Clı́nic per la Recerca Biomèdica, N.B. received a grant from Ministerio de Educación y Cultura (PN96-46136692), and M.P. received a grant from Hospital Clı́nic Universitari. J.L.P. and R.M.M. are Visiting Scientists from the Instituto Nacional de la Nutrición Salvador Zubiran and Fundación Clı́nica Médica Sur, Mexico D.F., Mexico. Portions of this investigation were presented at the 32nd Annual Meeting of the European Association for the Study of the Liver, London, April 9–12, 1997.
- Abbreviations:
- ALD
- aldosterone
- ADH
- antidiuretic hormone
- CO
- cardiac output
- SSC
- standard saline citrate
- GAPDH
- glyceraldehyde-3-phosphate dehydrogenase
- HR
- heart rate
- MAP
- mean arterial pressure
- mUOsm
- minimum urinary osmolality
- PCR
- polymerase chain reaction
- UADHV
- urinary excretion of ADH
- TPR
- total peripheral resistance
- UALDV
- urinary excretion of aldosterone
- UOsm
- urine osmolality
- UNaV
- urine sodium
- Received July 16, 1998.
- Accepted November 11, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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