ABSTRACT
Aim To study on the diuretic effect of a phenylphthalazines compound PU1424 and its influence on electrolyte balance, glucose and lipid metabolism, hepatic and renal functions.Methods Male Sprague Dawley rats were randomly divided into solvent control group,PU1424 treated group and HCTZ treated group.Urine was collected per 6 h and blood samples were collected at the end of drug administration.Urinary osmolality was measured by Freezing Point Osmometer;urea concentration was measured by Urea Detection Kit;ion level, blood glucose level, blood lipid level, hepatic and renal function were analyzed by Automatic Biochemical Analyzer.Results Compared to the solvent control group, and urine output of rats treated with PU1424 and HCTZ was increased as 1.52 times and 1.78 times and water intake increased as 1.42 times and 1.56 times respectively.Urine osmolalities were decreased as 61.5% and 50.4% of the control group, and urine urea concentration was decreased as 57.1% and 56.8% of the control group.Urinary electrolytes were decreased by administration of PU1424 and HCTZ compared to the intact plasma electrolytes.The blood glucose levels and blood lipid levels of rats treated with PU1424 had no changes, while the blood glucose and total cholesterol were increased by administration of HCTZ.The urea nitrogen, creatinine, alkaline phosphatase and total protein were intact by administration of PU1424 and HCTZ except the alanine/straw ration increased by HCTZ.Conclusion New diuretic candidate compound PU1424 displays significant diuretic effect with electrolyte balance, blood glucose level, blood lipid level, hepatic and renal function intact.
ABSTRACT
AIM: Aquaporin 3 ( AQP3 ) water channel expressed in the kidney plays a critical role in the urine concentrating mechanism. Mice with AQP3 deletion show a urinary concentrating defect. To better characterize this defect, we studied the influence and mechanism of an acute urea load in conscious AQP3 - null and wild - type mice. METHODS:Urine was collected and assayed every 2 h, from 2 h before (baseline) to 8 h after the urea load. Urine volume, urine osmolality and urea concentration were measured. RNA was isolated from the whole kidney and real - time PCR was carried out using a LightCycler. Total protein of UTs was assayed from kidney tissue by Western blotting. RESULTS: Mice of both genotypes excreted the urea loaded in ～ 4 h with the same time course. Despite their low baseline, the AQP3 - null mice raised their urine osmolality and urea concentration progressively after the urea load to the values almost equal to those in wild - type mice at 8 h. In contrast, urine non - urea solute concentration did not change. Urine volume fell in the last 4 h to about one - fourth of basal values. The urea load strongly upregulated urea transporter UT - A3 expression in both genotype mice. CONCLUSION: These observations show that lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute - selective response results from the capacity of AQP3 to transport not only water but also urea, suggesting a novel role for AQP3 in non - urea solute concentration in the urine.