bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Cell Volume in a Human Proximal Straight Tubule
Authors: Stapleton Bruder , Linshaw Michael A.
Published: November 2008

A single human proximal straight tubule, isolated from a nephrectomy specimen, was held between two micropipets with both ends tightly crimped. In 10-3 M p-aminohippurate, a visible lumen appeared indicating fluid secretion and tubule viability. The lumen was then allowed to collapse. We blocked active cation transport with ouabain and assessed changes in cell size by measuring the outer diameter of the nonperfused tubule. In ouabain and in a 6-g% protein bath, tubule size increased 23% above control, increased further when bath protein was removed and increased enormously when the tubule basement membrane was removed with collagenase. Cell size of the human proximal straight tubule in ouabain is determined to a major extent by passive transmembrane forces.
Effect of Triamterene on the Mammalian Distal Tubule in vivo
Authors: Lacy Frank B. , Dobyan Dennis C. , Jamison Rex L.
Published: November 2008

Using the recollection micropuncture technique it was demonstrated that the intragastric administration of triamterene significantly reduced the fraction of filtered potassium remaining (from 27 to 17%) and enhanced the fraction of filtered sodium remaining (from 3.6 to 7.9%) at the end of the accessible distal tubule in 7 rats. Fractional delivery of water, sodium and potassium to the distal tubule was not significantly altered. Urinary potassium excretion was reduced (from 17 to 7%). Similar experiments in 6 control rats disclosed no significant changes in the foregoing variables. In these experiments the principal effect of triamterene in vivo was an inhibition of potassium secretion in the distal tubule. An ostensible inhibitory effect on sodium reabsorption in the distal tubule was not unequivocally established.
Effect of Indomethacin on Renal Function Before and After Release of 24 Hours Unilateral Ureteral Ligation
Authors: László Katalin , Juszkó Julianna , Bálint Peter
Published: November 2008

In the anaesthetized dog during and 1 h after release of 24 h unilateral ureteral ligation (UUL) renal blood flow (RBF) decreased to 48 and 43%, respectively, as compared with normal controls. Radioactive microspheres revealed an inward distribution of RBF inasmuch as the ratio outer/inner cortical perfusion (OC/IC) dropped from a control value of 79/21 to 57/43 and 50/50 before and after release, respectively. In normal dogs inhibition of prostaglandin production by indomethacin caused a decrease of RBF with outward distribution, OC/IC amounting to 85/15. Indomethacin treatment in dogs with 24 h UUL led to a further 50% decrease in RBF with a nearly proportional reduction in outer and inner cortical perfusion, with OC/IC ratios amounting to 79/21 before and 74/26 after release. It is assumed that in the ligated kidney prostaglandins produced in the medulla are not transported by the tubular fluid to the outer cortical zones and only exert their dilating effect on the inner cortical, i.e., juxtamedullary, vessels.
Effects of Acetazolamide on Renal Ammoniagenesis in Dogs
Authors: Risquez Alvaro , Hernandez William , Preuss Harry G.
Published: November 2008

Renal ammonia production was followed in vivo in 7 dogs after the acute administration of acetazolamide. Acetazolamide at various doses decreased average renal ammoniagenesis to 55% of control and decreased ammonium excretion even more, to 18% of control. This discrepancy occurred because diffusion of ammonia into the urine was severely reduced while renal venous release was influenced little. Therefore, inhibition of ammonium excretion in dogs by acetazolamide took place because the drug both diverted ammonia from the urine and inhibited ammoniagenesis. Decreased renal ammoniagenesis could not be explained entirely by a decreased functioning mass, and it was not explicable on the basis of inhibited glutamyl transferase or stimulated glutamine synthetase in vivo or in vitro.
Early Effect of Triiodothyronine on Renal Handling of Potassium and Sodium in the Rat
Authors: Lo Chu Shek , Gerendasy Dan
Published: November 2008

The early effect of triiodothyronine (T3) on renal handling of K+ and Na+ in hypo-thyroid and euthyroid rats was studied. Individual rats were kept in metabolic cages. Sodium and potassium intake as well as urinary Na+/K+ ratio and excretion were determined daily for the first 2 days after one injection of T3 was administered to hypothyroid and euthyroid rats. Pre- and post-injection values for the urinary Na+/K+ ratios in the hypothyroid rats were consistently higher than the euthyroid rat. However, in both hypothyroid and euthyroid rats, no change in K+ and Na+ intake, K+ and Na+ excretion, and urinary Na+/K+ ratio was observed at 24 or 48 h after T3 injection. The results of these studies suggest the absence of an early response of aldosterone secretion to T3.
Differential Solubility and Subunit Composition of Rat Glomerular Basement Membrane
Authors: Price Robert G. , Taylor Sarah A. , Khalil-Manesh Farhad
Published: November 2008

Glomerular basement membrane (GBM) was prepared from 2- to 3-month-old Sprague-Dawley rats by differential sieving and sonication. 80% of the membrane was soluble in 1% sodium dodecyl sulphate (SDS) and 1% 2-mercaptoethanol. The soluble fraction was resolved into 15 bands in the molecular weight range 30,000 to 300,000 by SDS-polyacrylamide gel electrophoresis. The major bands present had apparent molecular weights of 100,000 and 148,000. Treatment of GBM with SDS alone solubilised mainly low molecular weight components (45,000–150,000) but when the residue was treated with SDS and 2-mercaptoethanol higher molecular weight material was solubilised. Partial solubilisation of GBM was also achieved with pepsin. Digestion for 18 h at 4°C resulted in 20% of the membrane being solubilised but this was increased to 55% at 10 °C. The amino-acid composition of pepsin-soluble GBM was more collagen-like than the residue remaining after enzyme digestion. Although the residue was more polar than whole GBM it still contained significant amounts of glycine and hydroxyproline and could be further sub fractionated with SDS into a soluble fraction, the amino acid content of which was similar to whole GBM and a collagenous residue containing 317 residues/1,000 of glycine. When pepsin solubilised GBM was subjected to horizontal electrophoresis in SDS-polyacrylamide slab gels the principal bands migrated in the pro-α-chain region. This material was heterogeneous and in addition to the principal components, 6 components with apparent molecular weights less than 95,000 were present together with high molecular weight material in the γ and β regions of the gel. The band pattern of the pepsin-insoluble material was similar although the intensities of some individual bands varied significantly from that of the pepsin-soluble material. Rat GBM can therefore be fractionated by treatment with SDS alone, SDS together with 2-mercaptoethanol and pepsin digestion. The data reported is compatible with the presence of a mixture of collagen-like and polar regions rather than a major single collagenous component (type IV collagen).
Specific Insulin Receptors in Rat Renal Glomeruli
Authors: Meezan E. , Freychet P.
Published: November 2008

The kidney is a major site of pathologic complications in diabetes mellitus including those affecting the basement membrane. Although several hypotheses of the etiology of renal diabetic microangiopathy involve effects of insulin on basement membrane metabolism, little is known about the localization or properties of insulin receptors in isolated renal glomeruli. We have incubated isolated glomeruli and tubules with 125I-insulin and examined the binding of the hormone to these purified renal subfractions. Glomeruli and tubules exhibited specific binding of 125I-insulin at 22 °C which increased with time and protein concentration. Nonspecific binding accounted for 20–35% of the total binding observed. At a concentration of 1 ng/ml 125I-insulin specific binding reached a plateau within 60–90 min at 22 °C. Unlabeled insulin competitively displaced 125I-insulin from its binding sites with 2.8 × 10-9 Minsulin inhibiting half of the initial binding to glomeruli while a 10-fold higher concentration of unlabeled insulin was required to achieve a similar inhibition of tubular binding. Insulin analogues were less potent than insulin itself in inhibiting the binding of 125I-insulin to both glomeruli and tubules in the order of relative potency: insulin > despentapeptide insulin > proinsulin indicating the specificity of the binding. Scatchard analysis of the competition binding data of 125I-insulin to glomeruli and tubules was consistent with two distinct binding sites and/or negative cooperativity between one class of receptor sites. The binding of 125I-insulin to the glomerular receptor(s) exhibited a higher affinity than that to the tubular receptor(s) which had a greater binding capacity. These two subunits of the nephron, therefore, contain insulin receptors with different binding properties which may serve different functions.
Proteolytic Degradation of the Glomerular Basement Membrane and Immunochemical Characterization of Split Products
Authors: Lubec G. , Förster O. , Coradello H. , Maxa E. , Pollak A.
Published: November 2008

Glomerular basement membranes (GBM) were isolated and subjected to enzymatic degradation with the protease trypsin (Serva), chymotrypsin (Serva), papain (Sigma), pepsin (Serva) and collagenase (Worthington) as well as a lysosomal preparation from glass adherent rat blood and peritoneal exudate cells. Split products were characterized by immunoelectrophoresis and cellulose acetate electrophoresis. Urine was obtained from healthy rats and rats with Masugi’s experimental glomerulonephritis, dialyzed and concentrated and applied on immunoelectrophoresis, using anti-GBM antibody from rabbit. Urinary GBM split products from healthy and nephritic rats showed two precipitation lines like digestion products obtained after chymotrypsin degradation. This finding was supported by characterizing individual antigenic degradation products obtained after inhibition of GBM degradation by the lysosomal preparation with ethylenediaminetetraacetic acid and Trasylol alone and in combination, as well as with o-phenanthrolin. It is concluded that GBM-antigens excreted into urine indicate limited digestion of GBM by chymotrypsin-type protease.
Mesangiolysis of Isolated Renal Glomeruli with the Formation of Lobular Sacs or Cysts
Authors: Krakower Cecil A. , Manaligod Jose R.
Published: November 2008

60% trichloracetic acid (TCA) will dissolve the cells and mesangial matrix of isolated renal glomeruli before it dissolves the basement membranes (BM). With the removal of the mesangial cells and matrix, the paramesangial BM stands out in sharp relief. It is thicker than that of the capillary loops and is provided with prominent ridges and spurs. These thick collars of BM now border the narrow channels left after the removal of the mesangium. The channels communicate with the capillary lumens. They widen asynchronously with the continued action of the TCA leading at first to more axial cavitation of the lobules of the glomerulus and finally to the conversion of these lobules into sacs or cysts. This is brought about by the unfolding of the capillaries within the investing sheath of BM which is common to the capillary loops and the widened stalks and intercapillary axial portions of the mesangium.
Different Antibody Response in Experimental and Spontaneous Glomerulonephritis
Authors: Wieslander Jörgen , Gygren Per , Heinegård Dick
Published: November 2008

The immune nephritis antibody response against the collagen and glycoprotein portions of the glomerular basement membrane (GBM) has been monitored by using either type IV collagen prepared from pepsin digests or a collagenase digest of GBM. Sheep immunized with GBM, according to Steblay, respond by developing antibodies directed against the collagen and the glycoprotein portions, respectively. Circulating antibodies directed against sheep GBM structures were not demonstrated until overt clinical disease with high serum creatinine values and proteinuria. Such antibodies could, however, be eluted from the kidneys, where they adsorbed in a linear fashion as demonstrated by immunofluorescence microscopy. In spontaneous human nephritis in Goodpasture’s syndrome, circulating antibodies were present at the time of diagnosis. These antibodies reacted only with the glycoprotein portion of the basement membrane, and not with the type IV collagen.
Glomerular Lesions in Patients with Late-Onset Cystinosis with Massive Proteinuria
Authors: Pabico Rufino C. , Partner Bernard J. , McKenna Barbara A. , Bryson Michael F.
Published: November 2008

3 siblings – 2 brothers aged 18 and 13 years, and 1 sister, aged 11 years – with adolescent or late-onset cystinosis presented with massive proteinuria. At the time their glomerular filtration rate was normal or only modestly diminished. Though glomerular injury was evident, renal tubular functional abnormalities were also present. Renal biopsy revealed histopathologic features typical of the nephropathic form of cystinosis with the Fanconi syndrome: polykaryocytosis, varying degrees of glomerular sclerosis, thickening and reduplication of basement membrane, fused foot processes, dilated tubules with altered epithelial cell features, and interstitial fibrosis. Fine granular deposits of C3 and IgM are irregularly distributed in the glomeruli, findings which have not been described in cystinosis. These deposits are possibly immune complexes being deposited in the glomeruli unrelated to the cystine-storage disease or they may represent a localized activation of the complement system induced by the glomerular injury of cystinosis.
Evolution and Characterization of Renal Immune Complexes Deposition in Mice Bearing a Syngeneic Tumor
Authors: Leyva-Cobian F. , Lamoureux G. , Rojo-Ortega J.M.
Published: November 2008

Immune complex deposition along the glomerular basement membrane (GBM) and in the mesangium in C57BL/6 mice bearing a transplantable syngeneic B16 melanoma is described. By immunofluorescence studies, IgG, IgM and C3 were found deposited along the GBM and the mesangium. Electron microscopy showed electron-dense deposits localized in GBM and mesangial matrix. The intensity of the immune complexes deposited in the glomeruli was correlated with progression of tumor size. In order to study the evolution of deposits, a monitoring protocol was designed. One group consisted of mice bearing B16 melanoma. They showed decreased immune complex deposition after tumor removal. Control mice inoculated with saline did not present immune complex deposition. Sham-operated mice bearing B16 melanoma showed progressive renal deposition of immune complexes. Immune complexes were made up of tumor antigen and antimelanoma antibodies and were partially characterized by elution, immunofluorescence and immuno-diffusion procedures. Antimelanoma antibodies eluted from kidneys of tumor-bearing mice were of IgG class and reacted with a soluble product extracted from B16 melanoma cells.
Glomerular Basement Membrane and Mesangial Matrix
Authors: Reale E. , Luciano L. , Kühn K. , Stolte H. , Brod J.
Published: November 2008

Perfusion fixation of the rat kidneys with aldehydes and alcian blue demonstrates within the glomerular mesangium various components displaying anionic binding sites. These are the surface coat of the mesangial cells, numerous mesangial microfibrils (probably glycoproteins), and polygonal particles (presumably proteoglycans). These particles lie close to the mesangial cells and form assemblies of various extension within the mesangial matrix as well. In addition, a discontinuous basement membrane can be recognized which surrounds the mesangial cells. In the hagfish glomeruli (fixed without cationic dye), a prominent layer of microfibrils is interposed between mesangial and endothelial cells. Both these cells show incomplete basement membranes.
Nonenzymatic Glycosylation of Glomerular Basement Membrane
Authors: Cohen Margo P. , Urdanivia Enrique , Wu Van-Yu
Published: November 2008

To test the hypothesis that increased nonenzymatic glycosylation contributes to the microangiopathic sequelae of diabetes, we examined the interaction of glucose with basement membranes in vivo and in vitro. The level of nonenzymatic glycosylation, determined by hydroxymethylfurfuraldehyde (HMF) generation, in glomerular basement membrane (GMB) collagen purified from rats with streptozotocin diabetes was significantly greater than that of nondiabetic GMB. Incubation of purified rat GBM and lens capsule basement membrane with [14C]-glucose in vitro resulted in the incorporation of [14C] into acid precipitable radioactivity in a reaction that was dependent on time, temperature, and glucose concentration. Glucose-dependent nonenzymatic glycosylation of GBM in vitro was documented by measurement of HMF generation after incubation with unlabeled glucose. These results provide direct experimental evidence that hyperglycemia, via nonenzymatic glycosylation, modifies the chemistry of proteins specifically involved in diabetic glomerulosclerosis.
Functional Adaptation to Reduction in Renal Mass: Renal Handling of Amino Acids by Isolated Perfused Remnant Rat Kidneys
Authors: Perez Guido O. , Epstein Murray , Rietberg Barbara , Horton Charles
Published: November 2008

To date, the renal handling of amino acids by remnant kidneys remains undefined. We have determined the renal handling of eight amino acids using the isolated perfused rat kidney. 6 normal and 22 partially infarcted rat kidneys (16 stage III [contra-lateral kidney removed], and 6 stage II [contralateral kidney left intact] were evaluated at perfusate amino acid concentrations approximately ten times normal plasma levels. Despite the reduction in glomerular filtration rate, the urinary excretion of most amino acids in remnant kidneys tended to exceed that of controls. Fractional amino acid excretion by both stage II and III kidneys tended to be or was higher than that of controls. The findings indicate that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased. Our observations suggest that the changes are unrelated to a functional adaptation to the uremic environment.
Treatment of Refractory Oral Erosive Lichen Planus with Topical Rapamycin: 7 Cases
Authors: Soria A. , Agbo-Godeau S. , Taïeb A. , Francès C.
Published: November 2008

Background: Chronic erosive oral lichen planus (CEOLP) is a painful disease. Topical steroids constitute the mainstay of treatment. Given the reports of a slightly greater risk of squamous-cell carcinoma, rapamycin may be a good candidate for recalcitrant CEOLP, as it has both immunosuppressive and antitumour properties. Objectives: To investigate the therapeutic effect and evaluate the blood absorption of topical rapamycin in patients with CEOLP. Patients and Methods: We carried out an open prospective study: 7 women with CEOLP applied topical rapamycin (1 mg/ml) on oral erosive lesions twice a day for 3 months. Four patients also had erosive vulvar lesions and applied the same solution on both mucosae. We monitored blood sirolimus levels 15 days after the initiation of treatment. Complete remission was defined by the disappearance of oral erosions and partial remission when the surface of oral erosions was 50% less than the surface of the initial erosion. Results: At 3 months, 4 women had complete remission and 2 women had partial remission. One patient stopped treatment due to local discomfort. Only 1 woman had blood sirolimus levels that were detectable. Conclusion: Topical rapamycin may be effective in some cases of refractory CEOLP, with negligible absorption into blood and minimal side effects.
Functional and Structural Changes in the Rat Kidney by Long-Term Lithium Treatment
Authors: Christensen Sten , Hansen Bent Brandt , Faarup Poul
Published: November 2008

The relation between functional and structural renal changes induced by lithium was studied in rats during long-term treatment and after withdrawal of lithium. Administration of LiCl in the diet for up to 21 weeks caused marked polyuria associated with a significant lowering of renal concentrating ability assessed by dehydration and vasopressin tests. Plasma creatinine and plasma urea were not significantly changed by the treatment. Upon withdrawal of lithium water intake and concentrating ability were normalized within 4–8 weeks. Lithium caused focal light microscopic changes in the distal convoluted tubule and the collecting duct, consisting of nuclear and cellular polymorphism and, after prolonged treatment, dilatation of tubular lumens with tubular cell atrophy. These changes appeared later than the concentrating defect and persisted when lithium was withdrawn after prolonged treatment. No significant correlation was found between the degree of tubular changes and water intake or concentrating ability. It is concluded that the reversible diabetes insipidus induced by lithium in rats cannot be explained directly by the light microscopical changes observed in the distal part of the nephron, although the structural changes may be secondary to the polyuric state induced by lithium.
The Role of Plasma and Renal Renin in the Rise in Blood Pressure Following Unilateral Renal Artery Constriction
Authors: Atkinson Jeffrey , Kirchertz Ernst J. , Peters-Haefeli Lise , Lüthi Pierrette
Published: November 2008

Constriction of the artery to the remaining kidney of control rats uninephrectomized 24 h previously induced a sixfold rise in plasma renin level from 11 ± 1 to 60 ± 11 ng AI mh-1 h-1, a 43% decrease of renal cortical renin level, and a 21% rise of mean arterial pressure from 119 + 2 to 144 ± 3 mm Hg. Constriction of the artery to a renin-depleted kidney (with a renin level which was 5% of normal) was not followed by any significant increase in plasma renin level or mean blood pressure. Renin-depleted kidneys were produced by removing the clipped kidney from two-kidney one-clip hypertensive rats, 24 h before the experiment. Such a maneuver induces renin depletion but does not completely normalize blood pressure. When a large dose of frusemide (50 mg/kg i.p.) was injected immediately following removal of the clipped kidney, mean arterial pressure (117 ± 7 mm Hg) returned to control values 24 h later but again constriction of the remaining renal artery failed to induce a rise in plasma renin level or mean arterial pressure. By 7 days after removal of the clipped kidney, plasma renin level and mean arterial pressure were normal and clipping of the remaining kidney (in spite of the fact that kidney renin level was still low) now produced a wave of renin release and an increase in mean arterial pressure. These results suggest that the initial, rapid increase in mean arterial pressure following unilateral renal artery constriction is dependent on an increase in plasma renin level. Our results from animals with kidneys of varying renin levels suggest the existence of a cortical renin content of about 20% of normal below which the kidney is incapable of responding to renal artery constriction with significant renin release. Complete recovery of the renin (and blood pressure) response to clipping occurred when the renin content had reached about 75% of normal.
The Association of Renal Infarcts with Carotid Artery Catheters Used for Clearance Studies
Authors: Verani Regina R. , Brewer Eileen D. , Ince Ann , Bulger Ruth Ellen
Published: November 2008

Carotid arterial catheters, inserted for repetitive sampling of arterial blood, were associated with frequent renal infarcts in rats. Renal infarcts were not seen with jugular venous catheters alone.
Substance P-Induced Changes in Kidney Function in the Conscious Rat: Relation to the Renal Prostaglandin System
Authors: Kramer Herbert J. , Klingmüller Dietrich , Flachskampf Frank A. , Düsing Rainer
Published: November 2008

Infusion of substance P into the renal artery was previously shown to cause a significant natriuresis which was associated with increased kallikrein excretion. Since the renal kinin and prostaglandin (PG) systems may be interrelated, the present study was performed to investigate the effects of substance P on renal function and its potential interaction with the renal PG system in the conscious rat. 24 female Sprague-Dawley rats were infused intravenously with substance P (1 ng · min-1 · kg-1 body weight) and the body weight was kept constant by an intravenous infusion of 0.45% saline. Substance P had no effects on arterial blood pressure, glomerular filtration rate (GFR) and 125I-hippuran clearance in the absence or presence of indomethacin (INDO). Basal UPGE2 V was unaltered by substance P infusion but was suppressed by INDO before and during substance P by 80 and 88%, respectively. Substance P raised urinary flow rate (V) by 105%, CH2O by 96%, UNaV by 378%, UKV by 48% and UPO4V by 147% (p < 0.001). Although INDO significantly suppressed V, CH2O, and UNaV during all collection periods, it did not affect absolute UPO4V and UKV and the relative rise in V, CH2O, and UNaV induced by substance P. Thus, the diuretic and natriuretic effects of substance P are not mediated by renal PG, but are partially blunted by INDO through increased distal absorption of sodium and water, INDO has no effect on substance P-induced alterations in proximal tubular function.
The Role of the Renin-Angiotensin System in the Hormonal and Renal Responses to Tilt in Normal Man
Authors: Mimran Albert , Deschodt Gérard
Published: November 2008

Head-up tilt is associated with rapid increases in total peripheral and renal resistance and falls in the urinary excretion of water and sodium. The influence of the acute oral administration of the converting enzyme inhibitor captopril (50 mg) on the consequences of 60° head-up tilt were assessed in 6 normal subjects on unrestricted sodium intake. Captopril did not modify the responses of arterial pressure and heart rate to tilt, although a significant decrease in supine mean arterial pressure was induced by captopril. In addition, the agent blunted by 50–60% all the changes in renal hemodynamics and urinary excretion of water and electrolytes except for that of the fractional excretion of sodium. Urinary kallikrein activity which markelly fell and plasma aldosterone concentration which increased during tilt before captopril were not affected after administration of the drug. These studies indicate that angiotensin might mediate at least in part the renal hemo-dynamic and functional responses to tilt in normal man and is the primary determinant of the aldosterone stimulating effect of tilt.
Glycoprotein Synthesis of Renal Collecting Duct Epithelium Cultured as Globular Bodies
Authors: Minuth Will W.
Published: November 2008

Cortical kidney explants from newborn New Zealand rabbits were cultured in Dulbecco’s minimum essential medium (DMEM) containing 10% fetal calf serum. Within 24 h the explants formed ‘globular bodies’ which were completely covered by a monolayered epithelium. The cells were differentiated and resembled collecting duct epithelium. By culturing the globular bodies in Dulbecco’s MEM with D-valine instead of L-valine, a monolayer of collecting duct cells was obtained and used for control experiments. For analysis and identification of synthesized glycoproteins, the globular bodies were incubated with various labelled carbohydrates and amino acids, and then fractionated. Glycoproteins secreted into the culture medium were not detected. Cell-associated glycoproteins were found in crude membrane fractions and then extracted with Triton X-100 for column chromatography, SDS-polyacrylamide electrophoresis in 6 M urea, isoelectrofocusing, and two-dimensional electrophoresis. Two prominent glycoproteins containing galactose and glucosamine were synthesized during the spreading of the epithelium, with an apparent molecular weight of 150,000 and 85,000 (SDS-PAGE). The synthesized glycoproteins differ in their content of radioactive glycoprotein precursor and leucine. The 85,000 dalton monomer glycoprotein has an isoelectric point of 3.5 and was identified by two-dimensional electrophoresis.
Relationship between Sodium Transport and Oxygen Consumption in the Isolated Perfused Rat Kidney
Authors: McTigue Maureen , Ting George O. , Weiner Michael W.
Published: November 2008

The purpose of the present experiments was to determine the relationship between Na+ transport and 02 consumption of the perfused rat kidney in vitro. The ΔNa/ΔO2 ratio was calculated from the change in Na+ transport and the change in O2 consumption. Na+ transport was varied by lowering perfusion pressure or adding ouabain. Previous investigators have calculated the ΔNa/ΔO2 ratio for the kidney in vivo by combining all data points in each group of experiments. Using this approach, the ΔNa/ΔO2 ratio of the perfused kidneys was 66.3 + 22.0 for the low pressure perfusion experiments and 29.1 + 3.1 for the ouabain experiments. These values are at least as great as those reported for the kidney in vivo. The ΔNa/ΔO2 ratios were also calculated by determining the regression line for each individual kidney, and then obtaining the mean of these regressions. Using this approach, the ΔNa/ΔO2 ratio for the low pressure perfusion experiments was 37.0+7.4 and the ΔNa/ΔO2 ratio for the ouabain experiments was 20.3 + 1.7. These values are significantly lower than the ratios obtained by combining all data points. The ratio of absolute Na+ transport to absolute O2 consumption (Na/O2 ratio) was 13.1 + 0.5 for control experiments. This value is considerably less than that obtained for the kidney in vivo. The extrapolated rate of O2 consumption in the absence of sodium transport (i.e. nontransport metabolism) was 40–63% of the control rates of oxygen consumption; this is a much higher fraction of ‘nontransport’ metabolism than in the kidney in vivo. It is concluded that the metabolic efficiency of the perfused kidney is considerably less than that of the kidney in vivo. Furthermore, the present results cast doubt on the usefulness of the ΔNa/ΔO2 ratio as in index of efficiency of Na+ transport by the kidney.
Renal Denervation and Sodium Balance in Young Spontaneously Hypertensive Rats
Authors: Herlitz Hans , Ricksten Sven Erik , Lundin Stefan , Thorén Peter , Aurell Mattias , Berglund Göran
Published: November 2008

In 7-week-old male, spontaneously hypertensive rats (SHR) and matched normotensive control rats, Wistar Kyoto Rats (WKY), a bilateral renal denervation was performed. In two additional groups of rats a sham denervation was done (SHRS, WKYS). The animals were then kept in metabolic cages during a 10-day period during which sodium intake, urine volume, urinary sodium excretion, fecal sodium excretion, urinary aldosterone excretion and plasma renin activity were determined. Fractional urinary excretion of sodium was higher in the denervated SHR (p < 0.1) and WKY (p < 0.05) during the first 3 days after denervation, but during the following 3-day periods no difference between denervated and sham-operated groups was noted. The difference in fractional urinary excretion of sodium initially was due to a diminished urinary sodium excretion in the sham-operated groups since both SHRS and WKYS exhibited a significant increase between the first and the last 3-day period. Urine volume increased significantly in both SHR and WKY after denervation. Urinary aldosterone excretion on the 7th day after denervation was significantly lower in SHR compared to WKY, but there was no significant difference between the denervated and sham-operated groups. PRA was also significantly lower in SHR but no significant decrease was seen after denervation.
Effect of Castration on Urinary N-Acetyl-β-D-Glucosaminidase Levels in Male Beagles
Authors: Higashiyama Noboru , Nishiyama Shinya , Itoh Takako , Nakamura Masuhisa
Published: November 2008

Urinary N-acetyl-β-D-glucosaminidase (NAG), a sensitive marker for renal damage, was much higher in male beagles than in females. The daily output of NAG into urine in male beagles was almost three times that in females. Following bilateral vasectomy or castration, marked decreases occurred in urinary NAG output. These results led to the conclusion that the high urinary NAG output in male beagles is largely due to an admixture of secreted fluid from the gonadal system in the bladder. Thus, when using beagles for nephrotoxicity studies with NAG as a parameter, females are preferable.
Renal Handling of Endogenous Lysozyme in the Rat
Authors: Cojocel Constantin , Baumann Karl
Published: November 2008

Quantitative studies of endogenous lysozyme (low molecular weight protein) were performed in rats. Urine and plasma concentrations of lysozyme and inulin were measured spectrophotometrically. An improved lysozyme assay (standard curve established by using egg white-lysozyme) enabled us to determine the mean plasma concentration of endogenous lysozyme (4.4 µg· ml-1) and the urinary concentrations of endogenous lysozyme (between 0.1 and 3.8 µg · ml-1. The urinary concentrations of endogenous lysozyme were found to be dependent on urinary flow rate. High urinary concentrations (ULy) were found at low urinary flow rates (V). The excreted amount of endogenous lysozyme (ULy·V) was independent of urinary flow rate and yielded a constant value of 0.02µg·min-I. Mean glomerular filtration rate (GFR) was 1.2 ml- min-1 while clearance of endogenous lysozyme averaged 0.0039 ml · min-1. Inhibition of endogenous lysozyme reabsorption by cytochrome c was used to estimate the glomerular sieving coefficient of endogenous lysozyme in clearance experiments. CLy/GFR increased from a mean value of 0.0053 in control rats to 0.8 at maximal inhibition of tubular reabsorption of endogenous lysozyme by cytochrome c. Knowing the glomerular sieving coefficient, GFR and the lysozyme concentrations in plasma and urine samples, the filtered, excreted and reabsorbed lysozyme amounts could be calculated: 0.5% excreted and 99.5% reabsorbed. Reabsorbed endogenous lysozyme is stored in the kidney in high amounts (1,983 µg · g-1 kidney).
Indomethacin Inhibits Renal Functional Adaptation to Nephron Loss
Authors: Hahne Bengt , Selén Göran , Erik A. , Persson G.
Published: November 2008

Immediately after unilateral nephrectomy, the glomerular filtration rate (GFR) and urinary excretion rate increase in the remaining transplanted rat kidney. In a previous study, we found that GFR in a transplanted kidney was reduced through an activation of the tubuloglomerular feedback control. Excision of the rat’s own remnant kidney then reduced feedback sensitivity and thereby allowed GFR to rise. The present study aimed at investigating whether prostaglandins are involved in this functional adaptation. Clearance and micropuncture experiments were performed before and after administration of indomethacin and after subsequent unilateral nephrectomy. GFR and the urinary excretion rate of electrolytes and water were measured. From proximal tubular stop-flow pressure (PSF) measurements the feedback characteristics were determined as the maximal stop-flow pressure response (ΔPSF) to an increase in distal flow and the turning point (TP), i.e. the end proximal flow rate that caused 50% reduction of ΔPSF. The results showed that following nephrectomy the tubuloglomerular feedback sensitivity was decreased, with an increased TP and reduced ΔPSF. Pretreatment with indomethacin (2 mg/kg BW) prevented not only the change in feedback sensitivity at nephrectomy but also the rise in GFR. These results suggest that the prostaglandins play a possible role as one link in the chain of adaptive events occurring immediately after nephron loss.
Permselectivity: Relation between Foot Process Simplification and Macromolecular Configuration
Authors: Luke, III Robert L.
Published: November 2008

The simplification of the foot processes of the glomerular epithelial cells is the structural hallmark of proteinuria in nephrotic man and animals. The increased shear force in a filtrate funnelled within the lamina densa to simplified slit pores may decrease the friction of macromolecules which are prolate ellipsoids (cigar-shaped). The permeability of rigid long narrow proteins such as albumin, transferrin and immunoglobulin G may selectively increase when the slit pore is converted from a wide serpentine to a straight narrow space.
Effect of a Subtotal Nephrectomy on the Excretion of Urinary Alanine Aminopeptidase and Gamma Glutamyltransferase in the Male Wistar Rat
Authors: Stoykova S. , Philippon C. , Labaille F. , Prevot D. , Mondorf A.W. , Manuel Y.
Published: November 2008

The study of alanine aminopeptidase (AAP) and gamma glutamyltransferase (GGT), two integral components of the brush border membrane of the proximal kidney tubule, has generated considerable interest for research on the nephrotoxicity of drugs. AAP and GGT activity in urine correlate strongly. The three phases after a subtotal nephrectomy can be described as follows: the first phase, lasting 1 month, is characterized by an abrupt decrease of 70% in AAP and GGT activity, corresponding to the excised kidney mass. During the second phase, a partial recovery occurs representing nearly 50% of the AAP and GGT activity in the control group (30th to the 75th day after nephrectomy). These activities begin to decrease slightly in the third phase until the end of the experiment. In terms of remaining kidney mass, the results demonstrate a twofold increase of the AAP and GGT activity. The same phenomenon can be seen in the excretion of creatinine, except that the compensatory activity is multiplied by four in the remaining kidney. Good correlations between AAP activity, GGT activity, urinary creatinine, 24-hour urine volume, and 24-hour creatinine output are found in both experimental and control groups.
Angiotensin II Effects upon Glomerular Intracapillary Volume in the Rat
Authors: Fujiwara Yoshihiro , Kikkawa Ryuichi , Kitamura Eisaku , Takama Toshiro , Shigeta Yukio
Published: November 2008

The direct action of angiotensin II on renal glomeruli was quantified by measuring extracellular space in isolated, decapsulated rat glomeruli using 14C-inulin. The glomerular inulin space significantly decreased when treated with 0.1 nM to 1 µM of angiotensin II. The decrease was dose-dependent and blocked by 1-Sar, 8-Ile angiotensin II. Since the glomerular intracapillary space seems to occupy the majority of the extracellular (inulin) space in decapsulated glomeruli, these results suggest that angiotensin II decreases the glomerular intracapillary volume. This action of angiotensin II may lead to a reduction in glomerular filtering surface area, and thus, in the ultrafiltration coefficient.
Function of the Isolated Spontaneously Hypertensive Rat Kidney after Blood Pressure Reduction
Authors: Steele Thomas H. , Gottstein Jeanne H. , Challoner-Hue Laura
Published: November 2008

We treated 20-week-old spontaneously hypertensive rats (SHR) with either placebo or hydralazine, reserpine and hydrochlorothiazide for 1 month. Mean arterial pressure in treated SHR averaged 113 ± 7 mm Hg (mean ± SE), compared to 162 ± 12 mm Hg in animals receiving placebo (p < 0.01). Glomerular filtration rate (GFR) and sodium excretion were similar in both groups. In isolated perfused kidneys, the GFR and sodium excretion were significantly greater in the treatment group than in the placebo group at a perfusion pressure of 140 mm Hg (p < 0.01). Renal vascular resistance (RVR) of kidney from treated SHR was no different from RVR of kidney from placebo SHR. Hydralazine (6 mM) and diazoxide (4 mM) increased the GFR and sodium excretion of isolated SHR kidney perfused at 140 mm Hg (p < 0.05), but decreased RVR significantly (p < 0.05). We conclude that prolonged antihypertensive treatment renders higher GFR values to isolated SHR kidneys perfused at 140 mm Hg, with sodium excretion varying in proportion to the GFR. The addition of vasodilators to the perfusate of isolated SHR kidneys partially reproduced these changes, but only at extremely high concentrations unlike to be attained in vivo.
Age-Related Changes in Rat Glomerular Basement Membrane Components Solubilised with Pepsin
Authors: Khalil-Manesh Farhad , Price Robert G.
Published: November 2008

The proportion of glomerular basement membrane (GBM) solubilised following pepsin treatment increased with age when the digestion was carried out at 4°C, but remained constant at 50% of the membrane when the digestion was carried out at 10°C irrespective of rat age. Amino-acid analysis of the solubilised material indicated that it became more collagen-like with age, as judged by the increase in glycine, hydroxyproline and hydroxylysine content, if the digestion was carried out at 10 °C. Polyacrylamide gel electrophoresis of pepsin-solubilised material demonstrated that components with apparent molecular weights of 180,000, 160,000 and 130,000 increased in intensity with age. Components with apparent molecular weights < 85,000 were only present in pepsin-soluble material prepared from GBM isolated from young rats. The intensity of the bands in the pro-α-region varied with age and some procollagen-like material was not solubilised by pepsin treatment. These studies confirm that aging of rat GBM is characterised by an increase in the proportion of the collagenous components present in rat GBM.
Comparative Physiology of the Renal Proximal Tubule
Authors: Beyenbach Klaus W.
Published: November 2008

The comparative physiology of the renal proximal tubule (PT) is reviewed in the context of vertebrate evolution and vertebrate strategies of salt and water balance. Though extrarenal machanisms of salt and water balance contribute importantly to extracellular fluid (ECF) homeostasis in the lower vertebrates, the kidney acquires these functions with evolutionary progress and becomes the dominant organ of ECF homeostasis in mammals. In acquiring the major responsability over the ECF compartment the kidney favored filtration-reabsorption as the preferred mechanism for the rapid turnover of ECF with the advantage of providing quick renal regulatory responses. In spite of this specialization the structure and function of the PT do not appear to have undergone major evolutionary changes. In present-day vertebrates the PT remains as an immensely diverse transport epithelium with impressive capacities for both reabsorptive and secretory work, as exemplified by the mammalian PT with mostly reabsorptive functions and the PT of aglomerular kidneys with mostly secretory functions. The recent evidence for NaCl and fluid secretion in the PT of, unexpectedly, glomerular kidneys is consistant with the functional diversity and the conservative nature of evolution in the case of the PT.
Endocrine Control of Renal Handling of Solutes and Water in Vertebrates
Authors: Nishimura Hiroko
Published: November 2008

Hormones influence renal function by both extrarenal and intrarenal mechanisms. Extrarenal mechanisms include the effects through systemic hemodynamic and neural pathways, whereas intrarenal mechanisms can be largely divided into the effects on intrarenal hemodynamics and those on tubular transport epithelia. Neurohypophysial hormones and the renin-angiotensin system appear to act primarily on systemic and preglomerularvasculature in primitive vertebrates, while direct tubular action appears to have evolved at a later stage of phylogeny. Although aldosterone is an essential hormone for fluid mineral balance in mammals, the action of mineralocorticoids on tubular Na transport has not been established in nonmammalian tetrapods. In bony fishes in hyperosmotic environments, cortisol accelerates active Na extrusion from the gill. In contrast, prolactin is important for maintaining low osmotic water permeability of the transport epithelia in fishes in hypoosmotic media. Thus, both function and site of hormone action appear to have changed during the evolution of vertebrates interacting with changing environments, and in response to the demands from other bodily functions. Furthermore, evolution of interactions, at the cellular level, between systemic and locally formed hormones such as prostaglandins, kinins, and perhaps angiotensin may have developed more elaborate controlling systems of renal handling of solutes and water.
Long-Term Recovery of Superficial and Deep Glomeruli after Acute Renal Failure Evoked by Warm Ischemia
Authors: Källskog Ö. , Hellström I. , Rissler K. , Wolgast M.
Published: November 2008

A study was made on the number of glomeruli in the outer cortex, midcortex, and inner cortex 4 weeks after 45min of warm ischemia, using alcian blue to stain functioning glomeruli. During this time the stainable glomeruli in the kidney as a whole had decreased in number from 32,000 to 16,800. The superficial glomeruli were reduced by only about 30%, whereas in the juxtamedullary zones the number of functioning nephrons were reduced by 80%. This shows that the juxtamedullary nephrons are the most susceptible to degeneration in the recovery phase of acute renal failure caused by ischemia. The decrease in the number of glomeruli was accompanied by a reduction in total glomerular filtration rate to about the same extent. In contrast, the kidney weight was reduced by only about 20%, suggesting compensatory hypertrophy of the remaining tubules. Fluid reabsorption, urine osmolality, and potassium-secreting ability also remained decreased. The contralateral kidney responded with a compensatory hypertrophy and an increase in glomerular filtration rate, whereas the number of glomeruli in the cortex as a whole and in the individual cortical zones in this kidney remained the same as in control kidneys. It is suggested that the trapping of red cells in the juxtamedullary circulation seen soon after restoration of circulation to kidneys subjected to warm ischemia will also cause a further degeneration of the juxtamedullary nephrons.
Micropuncture Study of the Superficial Nephron of Cercopithecus aethiops
Authors: Wong Norman L.M. , Reitzik Monty , Quamme Gary A.
Published: November 2008

Clearance and micropuncture experiments were performed on male Cercopithecus monkeys weighing between 2 and 4 kg to evaluate the function of the superficial nephron. The mean glomerular filtration rate was 4.47 ± 0.32 ml/min. The fraction of filtered sodium, potassium, calcium, magnesium, and phosphate remaining at the end of the accessible proximal tubule were 54 ± 3, 64 ± 4, 70 ± 3, 79 ± 5, and 39 ± 5%, respectively. The concentration of magnesium and calcium in the tubule fluid rose significantly along the length of the proximal tubule. The tubule fluid bicarbonate concentration was measured by determination of total CO2 with microcalorimetry. The tubule fluid to blood bicarbonate ratio fell to 0.48 ± 0.06 at the late proximal tubule collection site, as the tubule fluid to ultrafiltrable chloride concentration ratio rose to 1.08 ± 0.02. Thus, bicarbonate is reabsorbed in preference to chloride in the superficial proximal tubule of the monkey, to provide a potential driving force for water and salt absorption. By the time the tubular fluid reached the distal tubule sampling site, most of the filtered sodium potassium, calcium, magnesium, and chloride was reabsorbed, suggesting the loop of Henle as a major site of ion reabsorption. Segments beyond the distal tubule collection site reabsorbed little of the delivered ions. These studies indicate that the function of the superficial nephron resembles that of species previously studied, except that calcium reabsorption is demonstrably diminished in the proximal convoluted tubule relative to other mammals.