pituitrin and niravoline

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Aquaporin 6; Aquaporins; Ascites; Benzeneacetamides; Body Water; Demeclocycline; Diuresis; Diuretics; Humans; Kidney Tubules, Collecting; Liver Cirrhosis; Liver Cirrhosis, Experimental; Morpholines; Pyrrolidines; Rats; Receptors, Opioid, kappa; Receptors, Vasopressin; Spiro Compounds; Vasopressins

Topics: Animals; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Benzeneacetamides; Body Water; Demeclocycline; Diabetes Insipidus; Dogs; Humans; Kidney; Liver Cirrhosis; Liver Cirrhosis, Experimental; Loop of Henle; Pyrrolidines; Rats; Receptors, Opioid; Vasopressins; Water-Electrolyte Balance

kappa-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.

Topics: Aldosterone; Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Benzeneacetamides; Body Water; Body Weight; Carbon Tetrachloride Poisoning; Diuretics; Hemodynamics; Hormones; Hypothalamus; Kidney; Liver Cirrhosis, Experimental; Male; Osmolar Concentration; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; RNA, Messenger; Urodynamics; Vasopressins

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.. 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).. 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.. 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.

Topics: Analysis of Variance; Animals; Arginine Vasopressin; Ascites; Benzeneacetamides; Blood Pressure; Body Water; Diuresis; Heart Rate; Kidney; Liver Cirrhosis, Experimental; Male; Natriuresis; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; Vasopressins