scholarly journals Potent inhibition of biphasic tubular reabsorption of lithium by acetazolamide and foscarnet in rats

2020 ◽  
pp. 645-651
Author(s):  
Y Uwai ◽  
R Kondo ◽  
T Suzuki ◽  
T Kawasaki ◽  
T Nabekura
Keyword(s):  
Urinary Excretion ◽  
Proximal Tubule ◽  
Lithium Chloride ◽  
Renal Excretion ◽  
Large Fraction ◽  
Fractional Excretion ◽  
Tubular Reabsorption ◽  
High Affinity ◽  
Maximum Value ◽  
Potent Inhibition

Lithium is mainly excreted into urine, and a large fraction of lithium filtered through glomeruli is reabsorbed in the proximal tubule. However, the mechanisms responsible for lithium reabsorption remain unclear. We previously reported that the reabsorption of lithium was biphasic in rats, and that foscarnet inhibited lithium reabsorption with a high affinity type. We herein evaluated the effects of acetazolamide and foscarnet on the renal excretion of lithium in rats treated with lithium chloride at 2 doses. In rats intravenously injected with a bolus of 25 mg/kg lithium chloride, acetazolamide facilitated the urinary excretion of lithium, and increased the fractional excretion of lithium from 0.446 to 0.953, near the theoretically maximum value. At a dose of 2.5 mg/kg lithium chloride, the fractional excretion of lithium was 0.241 in control rats, 0.420 in rats administered acetazolamide, and 0.976 in rats administered acetazolamide and foscarnet. These results showed the potent inhibition of lithium reabsorption by acetazolamide and foscarnet in rats. And, it was exhibited that the effects of acetazolamide on lithium reabsorption differed with the dosages of lithium administered.

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Pharmacology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Yuichi Uwai ◽  
Tomohiro Nabekura
Keyword(s):  
Proximal Tubule ◽  
Lithium Chloride ◽  
Maleic Acid ◽  
Fanconi Syndrome ◽  
Collecting Duct ◽  
Bipolar Disorders ◽  
Fractional Excretion ◽  
Tubular Reabsorption ◽  
Pharmacokinetic Parameters ◽  
Renal Handling

Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Using samples of plasma and bladder urine during the mannitol infusion, renal parameters were determined. Pharmacokinetic parameters of lithium were obtained using samples during the lithium chloride infusion. Maleic acid decreased creatinine clearance and increased the fractional excretion of glucose and phosphate, suggesting the induction of Fanconi syndrome. In rats with Fanconi syndrome, plasma concentration of lithium was increased, and its renal clearance was decreased. No effect on the fractional excretion of lithium was exhibited. This study represents that the tubular reabsorption of lithium was impaired to the same degree with glomerular filtration in rats with experimental Fanconi syndrome and that the dysfunction of the tubular reabsorption of glucose and phosphate was more severe. It is possible that Fanconi syndrome inhibited the reabsorption of lithium at the proximal tubule and facilitated the reabsorption of lithium from the loop of Henle to the collecting duct.

scholarly journals Analysis of sex difference in the tubular reabsorption of lithium in rats

2021 ◽  
Vol 70 (4) ◽  
pp. 655-659
Author(s):  
Yuichi Uwai ◽  
Riku Yamaguchi ◽  
Tomohiro Nabekura
Keyword(s):  
Sex Differences ◽  
Lithium Chloride ◽  
Tubular Reabsorption ◽  
Female Rats ◽  
Pharmacokinetic Parameters ◽  
Phosphate Transporters ◽  
High Affinity ◽  
Male And Female Rats ◽  
Sodium Dependent ◽  
Low Rate

Lithium is used in the treatment of bipolar disorder. We previously demonstrated that two types of transporters mediate the tubular reabsorption of lithium in rats, and suggested that sodium-dependent phosphate transporters play a role in lithium reabsorption with high affinity. In the present study, we examined sex differences in lithium reabsorption in rats. When lithium chloride was infused at 60 µg/min, creatinine clearance and the renal clearance of lithium were lower, and the plasma concentration of lithium was higher in female rats. These values reflected the higher fractional reabsorption of lithium in female rats. In rats infused with lithium chloride at 6 µg/min, the pharmacokinetic parameters of lithium examined were all similar in both sexes. The fractional reabsorption of lithium was decreased by foscarnet, a representative inhibitor of sodium-dependent phosphate transporters, in male and female rats when lithium chloride was infused at the low rate. Among the candidate transporters mediating lithium reabsorption examined herein, the mRNA expression of only PiT2, a sodium-dependent phosphate transporter, exhibited sexual dimorphism. The present results demonstrated sex differences in the tubular reabsorption of lithium with low affinity in rats.

scholarly journals Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats

2021 ◽  
Vol 23 (1) ◽  
pp. 203
Author(s):  
Mariusz Flisiński ◽  
Andrzej Brymora ◽  
Natalia Skoczylas-Makowska ◽  
Anna Stefańska ◽  
Jacek Manitius
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Serum Insulin ◽  
Fractional Excretion ◽  
Urine Ph ◽  
Regular Diet ◽  
Male Wistar Rats ◽  
Excessive Consumption

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR < 3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade

2007 ◽  
Vol 293 (5) ◽  
pp. F1433-F1438 ◽  
Author(s):  
Jane Goddard ◽  
Neil R. Johnston ◽  
Allan D. Cumming ◽  
David J. Webb
Keyword(s):  
Urinary Excretion ◽  
Renal Excretion ◽  
Fractional Excretion ◽  
Receptor Activation ◽  
Double Blind Study ◽  
Receptor Blockade ◽  
Double Blind ◽  
Endothelin 1 ◽  
Wide Range ◽  
Etb Receptor

Evidence suggests that urinary excretion of endothelin-1 (ET-1) reflects renal ET-1 production and is independent of systemic ET-1 activity. The influence of ET receptors on urinary ET-1 excretion has not been studied in humans, yet peritubular ETB receptors are abundant within the kidney. We have studied the effects of acute ETA and ETB receptor blockade with BQ-123 and BQ-788, respectively, on urinary ET-1 excretion in a randomized, placebo-controlled, double-blind study in 16 subjects with a wide range of GFRs (15–152 ml/min). Plasma ET-1 concentrations (pET-1) and urinary ET-1 excretion rate (uET-1) at baseline correlated inversely with GFR ( R2 = 0.18 and 0.36, respectively, P < 0.01). However, changes in pET-1 after ET receptor antagonism were not related to changes in uET-1 ( R2 = 0.007, P = 0.18). pET-1 increased only after BQ-788, alone or in combination with BQ-123, consistent with ETB receptor-mediated clearance of ET-1 from the circulation. uET-1 was reduced only after BQ-788 alone [−4.7 pg/min (SD 5.5), P < 0.01]. Because BQ-788 also reduced GFR, fractional excretion of ET-1 (FeET-1) was calculated. FeET-1 fell after BQ-788 alone [−41% (SD 26%), P < 0.01] or in combination with BQ-123 [−40% (SD 29%), P < 0.01]. FeET-1 was not altered by placebo or BQ-123 alone. In conclusion, urinary ET-1 excretion does not appear to relate to the pool of plasma ET-1. Because of the short duration of this study, it is unlikely that ET receptor blockade had significant effects on renal ET-1 production. Therefore, the reduction in FeET-1 after ETB blockade appears to indicate that renal excretion of ET-1 is at least partly facilitated by ETB receptor activation.

SOME EFFECTS OF PERCHLORATE ON THE DISTRIBUTION OF 131-IODIDE

1965 ◽  
Vol 50 (2) ◽  
pp. 195-201 ◽  
Author(s):  
E. Schönbaum ◽  
E. A. Sellers ◽  
M.J. Gill
Keyword(s):  
Urinary Excretion ◽  
Renal Excretion ◽  
Kidney Tissue ◽  
Intraperitoneal Dose ◽  
Blood Radioactivity ◽  
Radioactivity Levels

ABSTRACT The distribution of an intraperitoneal dose of 131-iodide was studied in rats receiving perchlorate. The accumulation of radioactivity in the stomach, which occurred soon after injection in controls, was inhibited by perchlorate. Concurrent with this, radioactivity in blood was higher in perchlorate treated rats than in controls. After perchlorate, more radioactivity in kidney tissue and an elevated urinary excretion of the tracer was noted. After 24 hours, plasma radioactivity was lower in perchlorate treated rats than in controls. Increased renal excretion of 131I after perchlorate is, at least in part, due to higher blood radioactivity levels, probably because of decreased iodide space due to the action of perchlorate.

Renal effects of nitric oxide synthesis inhibition in cirrhotic rats

1994 ◽  
Vol 267 (6) ◽  
pp. R1454-R1460 ◽  
Author(s):  
N. M. Atucha ◽  
J. Garcia-Estan ◽  
A. Ramirez ◽  
M. C. Perez ◽  
T. Quesada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Excretion ◽  
Renal Plasma Flow ◽  
Tubular Reabsorption ◽  
Nitric Oxide Synthesis ◽  
Important Mediator ◽  
Experimental Liver Cirrhosis ◽  
Endogenous Nitric Oxide ◽  
And Control ◽  
Experimental Liver

In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.

Renal excretion of cephapirin and cephaloridine: Evidence for saturable tubular reabsorption

1979 ◽  
Vol 25 (6) ◽  
pp. 870-876 ◽  
Author(s):  
Annie Arvidsson ◽  
Olof Borgå ◽  
Gunnár Alvan
Keyword(s):  
Renal Excretion ◽  
Tubular Reabsorption

Renal nerves and postprandial renal excretion in the conscious monkey

1991 ◽  
Vol 261 (5) ◽  
pp. R1197-R1203 ◽  
Author(s):  
T. V. Peterson ◽  
B. A. Benjamin ◽  
N. L. Hurst ◽  
C. G. Euler
Keyword(s):  
Urinary Excretion ◽  
Nonhuman Primate ◽  
Nasogastric Tube ◽  
Sodium Excretion ◽  
Renal Denervation ◽  
Renal Excretion ◽  
Renal Nerves ◽  
Electrolyte Excretion ◽  
Macaque Monkeys ◽  
High Sodium

Experiments were performed in conscious macaque monkeys to determine if the renal nerves are important in mediating postprandial increases in renal fluid-electrolyte excretion in this species. Monkeys were given a high-sodium meal via a nasogastric tube. Consecutive 10-min urine samples were taken during the 30-min time of meal administration and then 180 min postprandially. The experiment was performed both before and 10-14 days after each animal underwent renal denervation. Diuresis and natriuresis occurred under both renal-innervated and -denervated conditions. However, the amounts of urine and sodium excreted were less after renal denervation. For the total 210 min of measurements obtained after the meal was started, cumulative urine output was 95.0 +/- 26.4 ml and sodium excretion 7.18 +/- 1.74 meq in innervated kidneys vs. 56.7 +/- 7.0 ml (a 40% decrease; P less than 0.005) and 4.84 +/- 0.99 meq (a 33% decrease; P less than 0.01) after denervation. These results demonstrate that the renal nerves are important in the nonhuman primate for eliciting the postprandial changes in urinary excretion secondary to intake of a high-sodium meal.

Diurnal variation in urinary excretion of calcium and strontium

1965 ◽  
Vol 162 (989) ◽  
pp. 458-472 ◽  
Keyword(s):  
Urinary Excretion ◽  
Renal Excretion ◽  
General Pattern ◽  
Calcium Content ◽  
Normal Diet ◽  
Calcium Excretion ◽  
Extrinsic Factors ◽  
Regular Rhythm ◽  
Male Subjects ◽  
Normal Calcium

A marked variation in the 4-hourly urinary excretion of calcium and strontium was demonstrated in two male subjects on normal diet and activity. The general pattern of excretion was not, however, the same in the two who differed also in their pattern of response to a regular dietary intake of milk 4-hourly. Further experiment on one subject showed that on a regular 4-hourly diet of his normal calcium content a regular rhythm for calcium excretion was manifest only when activity was also controlled by his confinement to bed. Excretion of calcium was correlated, but not undissociably, with that of sodium. A similar daily rhythm was elicited by a diet low in calcium ( < 100 mg/day). Renal clearance of calcium and strontium ran parallel with a variation of up to sevenfold within a 24 h period. The results indicate a natural nycthemeral* variation in renal excretion of calcium and strontium, but this natural rhythm may be obscured by extrinsic factors, such as muscular exercise and loading of an internal reservoir such as the ‘exchangeable pool’.

scholarly journals Altered reabsorption of protein by the renal cortex in rats treated with hypertonic saline or mannitol.

1975 ◽  
Vol 23 (10) ◽  
pp. 707-721 ◽  
Author(s):  
W Straus
Keyword(s):  
Acid Phosphatase ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Hypertonic Saline ◽  
Intravenous Injection ◽  
Plasma Clearance ◽  
Renal Cortex ◽  
Proximal Tubule Cells ◽  
Subcutaneous Injections ◽  
Tubule Cells

The reabsorption of horseradish peroxidase (HRP) by the proximal tubule cells of rat kidneys was investigated by measuring the concentration of HRP in total particulate fractions of the cortex 1/4 and 1 hr after intravenous injection, and by correlated cytochemical observations. When compared to the corresponding values of the control animals, the concentration of HRP 1 hr after injection was decreased approximately 10-fold in the renal cortex of rats which had received an intravenous injection of hypertonic saline or two subcutaneous injections of mannitol. The plasma clearance and the urinary excretion of HRP were not altered significantly after injection of hypertonic saline, but the plasma clearance was decreased and the urinary excretion increased after injection of mannitol. When the dose of injected HRP was varied, the reabsorption of HRP by the renal cortex was proportional to the dose in the experimental and the control animals. Cytochemical staining for peroxidase activity also showed that the phagosomes and phagolysosomes of the proximal tubule cells contained much less peroxidase in the experimental rats than in the control rats. After injection of mannitol, large vacuoles appeared in the proximal tubule cells. The vacuoles often contained peroxidase-positive granules (phagosomes) which varied in diameter from the limit of microscopic visibility up to several microns. Most of the vacuoles did not react for acid phosphatase activity, but lysosomes were often aggregated around the vacuoles and seemed to release acid phosphatase into the cytoplasm. Certain analogies between the reabsorption of protein and that of water by the proximal tubule cells are discussed.

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