pituitrin and Carbon-Tetrachloride-Poisoning

Topics: Animals; Aquaporins; Body Water; Carbon Tetrachloride Poisoning; Carrier Proteins; Ion Transport; Kidney Tubules, Proximal; Liver Cirrhosis, Experimental; Loop of Henle; Rats; Sodium; Sodium Channels; Structure-Activity Relationship; Vasopressins; Water-Electrolyte Imbalance

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

A decreased pressor response to endogenous vasoconstrictors, such as angiotensin II and vasopressin, is a characteristic finding in cirrhosis with ascites; this has been considered as partially responsible for the arteriolar vasodilation present in this disease. Previous investigations suggested that this abnormality is due to a post-receptor defect leading to altered intracellular Ca2+ mobilization. To assess this hypothesis, vascular responsiveness to angiotensin II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were measured in aortic rings and in primary cultured aortic vascular smooth muscle cells, respectively. The study was carried out in 43 control rats and 40 rats with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+ indicator, for continuous monitoring of intracellular Ca2+ concentration. A decreased constrictor response to angiotensin II was detected in cirrhotic aortic rings in comparison to control rings (increase in tension: 31 +/- 5 vs 79 +/- 14 mg, p < 0.005). No differences in intracellular Ca2+ concentration between cirrhotic and control cells were observed in basal conditions (104 +/- 6 and 100 +/- 3 nM, respectively). Angiotensin II administration to cirrhotic vascular smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid increase, followed by return to a sustained level significantly higher than the basal value. This response was identical to that observed in control vascular smooth muscle cells. Similar findings were obtained following vasopressin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Calcium; Carbon Tetrachloride Poisoning; Cells, Cultured; Liver Cirrhosis, Experimental; Male; Muscle, Smooth, Vascular; Rats; Rats, Wistar; Stimulation, Chemical; Vasoconstriction; Vasopressins

The concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP) and hormones of the renin-angiotensin axis were studied in male rats with carbon tetrachloride-induced hepatitis and the results compared to normal control animals. The rats with hepatitis exhibited lower concentrations of ANP, plasma renin activity (PRA), and angiotensin I (AI) than did the control animals. Plasma concentrations of AVP and aldosterone were not significantly different in the two groups. The results suggest that experimental hepatitis is associated with renal hyperperfusion together with reduction in atrial pressures.

Topics: Aldosterone; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver; Male; Radioimmunoassay; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System; Vasopressins