Urate reabsorption in proximal convoluted tubule of the rat kidney

1976 ◽  
Vol 231 (2) ◽  
pp. 509-515 ◽  
Author(s):  
EJ Weinman ◽  
D Steplock ◽  
WN Suki ◽  
G Eknoyan
Keyword(s):  
Rat Kidney ◽  
Isotonic Saline ◽  
Chronic Administration ◽  
Fractional Excretion ◽  
Significant Inhibition ◽  
Acute Administration ◽  
Fractional Rate ◽  
Low Sodium Diet ◽  
Urate Reabsorption

Urate reabsorption was examined in the rat utilizing clearance and in vivo microperfusion techniques. In control rats, the fractional excretion of urate averaged 12.5 +/- 1.3% of the filtered load, with 60-70% of perfused urate reabsorbed at 2 mm of perfused tubule length (urate efflux). Increasing the perfusion concentration of urate to 6, 12, and 25 mg/100 ml did not alter the fractional rate of reabsorption. The acute administration of chlorothiazide resulted in a fall in GFR and Curate such that the fractional excretion was unchanged from controls and averaged 13.3 +/- 2.0%, without an associated change in urate reabsorption from proximal perfusates despite the presence of significant inhibition of sodium and water reabsorption. By contrast, the chronic administration of chlorothiazide accompanied by a low-sodium diet resulted in a significantly lower fractions excretion rate of urate of 7.95 +/- 0.5% and a significant increase in reabsorption of sodium and water as well as urate from microperfusates, In control rats receiving an infusion of 5% mannitol in isotonic saline, urate secretion was demonstrated by the urinary precession of [2-14C]urate from [methoxy-3H]inulin following placement of these isotopes on the surface of the kidney. The additional infusion of chlorothiazide did not alter this pattern of isotope recovery in the urine.

Direct effects of endothelin in the rat kidney

1990 ◽  
Vol 258 (2) ◽  
pp. F397-F402 ◽  
Author(s):  
T. Katoh ◽  
H. Chang ◽  
S. Uchida ◽  
T. Okuda ◽  
K. Kurokawa
Keyword(s):  
Renal Artery ◽  
Rat Kidney ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Left Renal Artery ◽  
Dependent Manner ◽  
Direct Effects ◽  
Dose Dependent

In the present study, we tested the direct effects of endothelin (ET) on rat kidney in vivo. ET was infused into the left renal artery of anesthetized rats at a rate of 0.5, 5, 20, or 40 pmol/h. ET reduced ipsilateral urine volume (V), clearance of inulin (CIN), and clearance of p-aminohippuric acid (CPAH) in a dose-dependent manner. Thus ET at 20 pmol/h did not change V but decreased renal plasma flow (RPF) and glomerular filtration rate (GFR) by 27.6 +/- 14.3 and 30.8 +/- 10.4%, respectively, in the ipsilateral kidney. ET at 0.5 pmol/h was without effect and at 5 pmol/h had only minor effects on CIN and CPAH of ipsilateral kidney. At 40 pmol/h, ET reduced ipsilateral V, GFR, and RPF by 52.3 +/- 21.4, 58.4 +/- 14.5, and 72.5 +/- 10.6%, respectively. Filtration fraction and fractional excretion of Na remained unchanged during ET infusion. ET, 40 pmol/h, infused into the renal artery together with atrial natriuretic peptide (ANP) at a rate of 12 pmol/h reduced the ipsilateral V, GFR, and RPF by 33.2 +/- 6.3, 26.1 +/- 6.0, and 27.2 +/- 7.1%, respectively, decrements less than those with ET alone. When a calcium-channel blocker nicardipine was infused at a rate of 2.5 micrograms/h into the renal artery together with ET, 20 pmol/h, there was little change in the ipsilateral V, RPF, and GFR; ET, 40 pmol/h, with nicardipine did not change V and decreased GFR and RPF by 25.9 +/- 5.6 and 23.1 +/- 10.8%, respectively, decrements less than those without nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-1 adrenergic inhibition of kallikrein release from rat kidney cortical slices

1990 ◽  
Vol 258 (5) ◽  
pp. F1425-F1431
Author(s):  
J. P. Girolami ◽  
J. L. Bascands ◽  
P. Valet ◽  
C. Pecher ◽  
G. Cabos
Keyword(s):  
De Novo ◽  
Rat Kidney ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Sodium Diet ◽  
Kidney Slices ◽  
Low Sodium Diet ◽  
Rat Cortical Slices ◽  
Cortical Slices

Renal storage; release, and biosynthesis of kallikrein were studied using rat cortical slices. This model permitted the study of the direct effect of norepinephrine on the renal kallikrein system in the absence of changes in perfusion pressure. Kallikrein was measured by its kininogenase activity and its direct immunoreactive concentration. Under basal conditions, rat kidney cortical slices synthesize and release glandular kallikrein in vitro at a linear rate for up to 40 min. Kidney slices obtained from rats fed with a low-sodium diet (LS) released more kallikrein into the incubation medium than slices from rats under a normal-sodium diet (NS). Cycloheximide and incubation at 4 degrees C inhibited the release and the biosynthesis of kallikrein independently of the sodium diet. Addition of norepinephrine (NE, 10(-8)-10(-5) M) induced a similar dose-dependent inhibition of kallikrein secretion, which reached -27 +/- 8% in NS rats and -29 +/- 9% in LS rats with 10(-7) M NE. This inhibition of the secretion was associated with an increase in tissue kallikrein concentration in kidney slices from rats on both sodium diets. However, a significant inhibition of the calculated net de novo synthesis was only observed in LS rats. In both groups of animals the ratio of active to total kallikrein was unchanged. The inhibitory effect of kallikrein secretion by NE was never modified in the presence of the alpha-antagonist phentolamine (10(-6) M). In contrast the beta-antagonist propranolol (10(-6) M) prevented the inhibitory effect of 10(-7) M NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular blood flow after single nephron obstruction in the rat kidney

1986 ◽  
Vol 250 (1) ◽  
pp. F77-F85 ◽  
Author(s):  
G. A. Tanner ◽  
L. C. Knopp
Keyword(s):  
Blood Flow ◽  
Castor Oil ◽  
Enzyme Inhibitor ◽  
Rat Kidney ◽  
Chronic Administration ◽  
Acute Administration ◽  
Tubule Lumen ◽  
Single Nephron ◽  
Micron Diameter ◽  
High Doses

This study examined the effects of kidney tubule lumen obstruction on glomerular blood flow (GBF) in anesthetized rats. GBF was estimated using microspheres having 9 micron diameter and averaged 239 +/- 10 nl/min in normal nephrons of 41 control rats. Tubule blockade with either paraffin wax or castor oil produced identical results. GBF after 1-2 h of obstruction did not differ from normal. After 1 day, GBF averaged two-thirds of normal, and after 1 wk GBF averaged one-third of normal. The hemodynamic changes produced by obstruction for 1 wk were diminished by chronic administration of high doses of the converting enzyme inhibitor captopril or acute administration of the angiotensin antagonist saralasin. The results suggest that angiotensin contributes to the vasoconstriction produced by prolonged obstruction. Nephrons blocked with castor oil contained oil 1 wk later, had a GBF of 88 +/- 24 nl/min, and were atrophied. We conclude that chronic single nephron obstruction produces progressive vasoconstriction, that this response is in part angiotensin mediated, and that the end result is nephron atrophy.

Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by isolated perfused rat kidney

1992 ◽  
Vol 263 (2) ◽  
pp. R273-R278
Author(s):  
M. R. Lebowitz ◽  
A. M. Moses ◽  
S. J. Scheinman
Keyword(s):  
Arginine Vasopressin ◽  
Rat Kidney ◽  
Fractional Excretion ◽  
Metabolic Clearance ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Clearance Receptor ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30 min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to 417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than 0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were directly related to filtered AVP, and this relationship was not altered by ANP. ANP did not affect the total organ clearance or the renal metabolic clearance of AVP. The increase in GFR was associated with increases in renal vascular resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium excretion (P less than 0.001). UCAVP also increased when GFR was raised without ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP, acting through its biological receptor and not the clearance receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate increases potassium secretion by perfused rat kidney

1986 ◽  
Vol 251 (5) ◽  
pp. F873-F878
Author(s):  
M. Brezis ◽  
K. Spokes ◽  
P. Silva ◽  
F. H. Epstein
Keyword(s):  
Rat Kidney ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Metabolic Inhibitors ◽  
Metabolic Substrates ◽  
Fractional Excretion Of Sodium ◽  
Renal Oxygen Consumption ◽  
Perfused Rat Kidney ◽  
K Secretion

The effect of exogenous metabolic substrates on K+ secretion was evaluated in the isolated perfused rat kidney in the presence of 2-deoxyglucose and 2-tetradecylglycidic acid to inhibit utilization of glucose and fatty acids from endogenous sources. L-Lactate (15 mM) added to the perfusion medium enhanced renal oxygen consumption (4.0 +/- 1.1 mumol X min-1 X g-1 vs. 2.0 +/- 1.0 without lactate) while decreasing fractional excretion of sodium (19.3 +/- 2.4% vs. 47.3 +/- 1.8). L-Lactate markedly increased the fractional excretion of K+ to 181 +/- 29% compared with 68 +/- 12% without lactate (P less than 0.001). The poorly metabolized isomer D-lactate did not alter these parameters. The addition of alpha-ketoglutarate only slightly increased K+ excretion. In the absence of metabolic inhibitors and in the presence of glucose (5 mM), L-lactate also increased K+ excretion significantly more than did D-lactate (108 +/- 19% vs. 69 +/- 11, P less than 0.02). At the end of 90 min of perfusion with L-lactate medium, K+ concentration in the perfusate dropped from 4.7 +/- 0.05 to 3.2 +/- 0.2 meq/liter (vs. 3.8 +/- 0.1 meq/liter with D-lactate, P less than 0.005) without differences in glomerular filtration rate or sodium excretion. L-Lactate appears to increase K+ secretion by preferential metabolic stimulation of the distal tubule, a process that may help in vivo to prevent hyperkalemia in lactic acidosis.

scholarly journals Metabolic alterations produced in the liver by chronic ethanol administration. Comparison between the effects produced by ethanol and by thyroid hormones

1973 ◽  
Vol 134 (2) ◽  
pp. 523-529 ◽  
Author(s):  
Y. Israel ◽  
L. Videla ◽  
A. Macdonald ◽  
J. Bernstein
Keyword(s):  
Thyroid Hormones ◽  
Adenosine Triphosphatase ◽  
Chronic Administration ◽  
Chronic Ethanol ◽  
Ethanol Administration ◽  
Acute Administration ◽  
O2 Consumption ◽  
Adenosine Triphosphatase Activity ◽  
Liver Slices

1. Liver slices from rats treated with thyroxine show an increased rate of O2 consumption. The extra consumption, but not the basal respiration, can be abolished by ouabain. 2. Dinitrophenol is not effective in increasing the rate of O2 consumption of liver slices from thyroxine-treated animals but its effectiveness can be recovered in the presence of ouabain. 3. (Na++K+)-stimulated adenosine triphosphatase activity of liver was increased by administration of thyroxine in vivo. No changes were found in total Mg2+-stimulated adenosine triphosphatase activity. 4. Mitochondrial α-glycerophosphate dehydrogenase and microsomal NADPH oxidase activity were increased by both thyroxine and chronic ethanol treatment. 5. Liver slices from animals chronically treated with ethanol synthesize urea at an increased rate. 6. Mitochondrial size (section area) is markedly increased in the liver of animals chronically treated with ethanol. 7. Acute administration of ethanol in doses of 4 and 6g/kg significantly increases the uptake of 131I-labelled thyroxine by the liver. 8. Work reported here, along with results from other investigators, indicates marked similarities between the effects produced in the liver by chronic administration of ethanol and by thyroid hormones.

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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