bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Recovery from Metabolic Acidosis in the Rat: No Role for Glutamine Synthetase
Authors: Duong N. , Vinay P. , Khoury N. , Guern C. , Gougoux A.
Published: November 2008

The role of renal glutamine synthesis for the rapid decrease in renal ammonia-genesis occurring early in the recovery phase (24 h) of metabolic acidosis was studied in rats. L-Methionine-DL-sulfoximine (MSO), an irreversible inhibitor of glutamine synthetase, depressed the renal enzyme activity by 50% but did not impair the recovery from acidosis. Since extrarenal glutamine synthesis was decreased by this manoeuvre with lowering of blood glutamine, an intravenous load of L-glutamine sufficient to elevate blood concentration to 1 mM was superimposed on the MSO treatement. The glutamine load did not increase the ammoniuria. Infusion of glutamine alone to rats recovering from metabolic acidosis for 12–24 h did not change their ammoniuria. In contrast, glutamine administration together with HC1 produced a marked ammoniuric response in rats recovering from acidosis. Conversely, the administration of bicarbonate to chronically acidotic rats acutely depressed renal ammonia production. It is concluded that glutamine synthetase activity is probably not required for recovery from metabolic acidosis, and that the post-acidosis alkaline rebound occurring in the rat may play a direct role in suppressing the ammonia-genie pathway either by drastic reduction in mitochondrial permeability for glutamine or acute inhibition of intramitochondrial deamidation of this amino acid.
Plasma Kinin Levels in Acute Renovascular Hypertension in Dogs
Authors: Moore, Jr. Jack , Gagnon John A. , Verma Pritam S. , Sander Gary E. , Butkus Donald E.
Published: November 2008

The role of kinins in the hypertensive response to acute renal artery constriction (RAC) was examined in the dog. RAC resulted in an increase in systemic arterial pressure (SAP) from 144 ± 6 to 155 ± 4 mm HG (p < 0.05). Simultaneously, arterial plasma bradykinin decreased from 2.3 ± 0.2 to 1.4 ± 0.1 ng/ml (p < 0.01), while renal venous bradykinin remained unchanged (2.3 + 0.2 to 2.0 + 0.4 ng/ml, p > 0.05). At the same time urinary kallikrein decreased from 55 ± 6 to 33 + 4 milliesterase units (mEU)/min (p < 0.05), while urinary kinin decreased from 3.2 + 0.4 to 1.9 + 0.3 ng/min (p < 0.05). There was a significant correlation between the decrease in arterial bradykinin and the rise in SAP induced by RAC (p < 0.01). Administration of the dipeptidyl hydrolase inhibitor SQ20881 during RAC reduced angiotensin-converting enzyme levels from 578 + 86 to 10 + 0.0 mU/ml (p < 0.005). There was an associated increase in arterial bradykinin (1.4 + 0.1 to 5.8 ± 0.8 ng/ml, p < 0.001), renal venous bradykinin (2.0 + 0.4 to 5.7 ± 0.5 ng/ml, p < 0.005), and urinary kinin (1.9 ± 0.3 to 5.0 ± 0.7 ng/min, p < 0.01) in conjunction with return of SAP to control levels. Urinary kallikrein, however, remained depressed following SQ20881 (33 ± 4 to 30 ± 5 mEU/min, p > 0.05). These results suggest that (1) decreases in circulating BK may potentiate the vasoconstrictor effect of angiotensin II and contribute to the hypertension induced by RAC, and (2) urinary kallikrein is an unreliable marker of changes in plasma bradykinin in this model of hypertension.
Isolation and Characterization of a Microvascular Fraction from Rabbit Kidney Cortex
Authors: Helwig J.J. , Judes C. , Bollack C. , Mandel P.
Published: November 2008

Collagenasic dispersion of rabbit kidney cortex followed by centrifugation on discontinuous sucrose gradient, allowed the simultaneous isolation of a microvascular fraction and of glomerular and tubular fractions. The microvessels were characterized by an overall diameter of 22 µm and the presence of granular and smooth muscle cells. Measurement of cellular renin activity and the muscle specific enzyme creatine kinase showed that these vessels were arteriolar in nature and that they contained the preglomerular arterioles. The glomerular or tubular contamination rates were assessed by means of enzymatic markers. Thus, in the arterioles, potassium fluoride-resistant acid phosphatase was some 10 times lower than in the glomeruli. The specific tubular enzymes γ-glutamyl-transpeptidase and alkaline phosphatase were about 20 times lower in the arterioles than in the tubular fraction. The possibility of obtaining these fractions may facilitate many types of study on renal hemodynamic and glomerulo-tubular feedback control.
Role of Prostaglandins in the Production of Natriuretic Factor by the Isolated Rat Kidney
Authors: Cambier P. , Godon J.P.
Published: November 2008

The renal origin of natriuretic factor (NF) of high molecular weight (MW 45,000) has been previously demonstrated. Its role in the control of sodium excretion by the kidney has been strongly suggested. The aim of the present work was to study the relationship between NF and prostaglandins, which are known to modify the renal regulation of sodium. (1) The activity of NF, obtained by ultrafiltration and gel filtration from pooled plasma of salt-loaded rats, was tested on an isolated rat kidney perfused by a cell-free medium. A significant natriuresis was observed in the kidneys isolated either from normal rats or from indomethacin-pretreated rats after injection of NF. Moreover, a dose-response curve was obtained with increasing amounts of NF. (2) The ability of isolated rat kidney to produce NF was studied in two series of salt-deprived rats, the second series being pretreated with indomethacin. The production of NF by isolated kidneys was induced by addition of saline to the fluid perfusing kidneys isolated from normal or indomethacin-pretreated rats fed a salt-depleted diet. Before addition of saline, no natriuretic activity was detectable. After the addition of 0.9% NaCl, NF was only found in the perfusate from kidneys isolated from normal rats. Perfusate extracts from indomethacin-pretreated kidneys did not induce any significant rise in natriuresis. (3) Kidneys isolated from rats previously fed a free fatty acid-deficient diet and thus prostaglandin-depleted were unable to produce NF even if they were salt-loaded. Intraarterial perfusion of prostaglandin E2 restored their ability to release or secrete NF. It is concluded that the release or the synthesis of NF is only possible in the presence of prostaglandins. Its action is not influenced by prostaglandin inhibition or deficiency.
Tubular Reabsorption in Normal Renal Function
Authors: O’Connor W.J.
Published: November 2008

The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption:(1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorptionof Na. This would amount to the reabsorption by the tubules of a net reabsorbate of acomposition similar to Locke’s fluid. Fixed linkage of the reabsorption of a substance to thereabsorption of Na would be a very effective way of maintaining its plasma concentrationwithin a narrow range. The substance would be retained unless its plasma concentrationexceeds a threshold value and then small increase in plasma concentration determines itsexcretion. (2). The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals.Trying to see ‘how far the observed facts can be brought into accord with a theory’ reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.
Evaluation of Renal Function during Intrarenal Norepinephrine Infusion in Conscious Rats
Authors: Kleinjans Jos C.S. , Smits Jos F.M. , Kasbergen Carina M. , Van Essen Helma , Struyker-Boudier Harry A.J.
Published: November 2008

Previous studies have shown that intrarenal infusion of norepinephrine (NE) causes acute renal failure in anesthetized dogs and rats. We hypothesized that anesthesia prevents the kidney of escaping from the ischemic insult. In this paper, we report measurements of renal function parameters during acute as well as during chronic intrarenal NE infusion in conscious freely moving rats. Intrarenal NE application in doses of 4 and 36 µg/kg · h was performed via the suprarenal artery by means of subcutaneously implanted minipumps. During acute intrarenal NE infusion over a 2-hour period in anesthetized as well as conscious rats, renal blood flow (RBF) was determined by means of the pulsed Doppler flowmeter technique. During long-term NE administration for 5 days, glomerular filtration rate (GFR) was determined as clearance of 51Cr-EDTA and effective renal plasma flow (ERPF) as clearance of 125I-hippuric acid. Clearance measurements were performed on control day, and on the 1st and 4th day of intrarenal NE infusion; furthermore, on the 1st and 4th day after stopping the intrarenal NE infusion.Acute intrarenal administration of doses of NE higher than 12 µg/kg · h, in anesthetized rats immediately reduced RBF to zero levels. However, in conscious rats, neither acute nor chronic intrarenal NE application induced severe long-lasting reductions in GFR or RBF respectively ERPF at any dose of NE applied. Therefore, we conclude that no acute renal failure is induced during intrarenal NE infusion in conscious rats; this is probably due to protective neurogenic mechanisms which are relatively inactivated during pentobarbital anesthesia.
Effect of Loop of Henle Flow Rate on Glomerular Capillary Pressure
Authors: Briggs Josephine P.
Published: November 2008

Studies were performed in male Munich-Wistar rats weighing a mean of 100 g to evaluate further the hemodynamic effects of changing loop of Henle flow rate. When late proximal flow rate was varied by microperfusion from the late proximal tubule, single nephron glomerular filtration rate (SNGFR) measured in the early proximal tubule fell from 17.2 + 0.86 nl min-1 at a perfusion rate of zero to 11.8 + 0.88 nl min-1 at a perfusion rate of 14 nl min-1. Further increases in loop flow did not further depress SNGFR. Glomerular capillary pressure (Pgc) was measured directly in superficial glomeruli while loop of Henle flow was varied. Elevating loop flow was followed by a rapid decrease in Pgc, which was reversible when flow was reduced. The mean response to maximum stimulation was a decrease in Pgc of 6.6 + 0.7 mm Hg, and the response was close to maximum at a perfusion rate of 14 nl min-1. Parallel changes in stop-flow pressure were observed. These findings, together with previous observations that increasing loop of Henle flow results in decreased single nephron blood flow, permit the conclusion that the dominant vascular response to elevated loop of Henle flow is constriction of the afferent arteriole.
Glomerular Albumin Leakage and Morphology after Neutralization of Polyanions. I.
Authors: Assel Eveline , Neumann Klaus-Hinrich , Schurek Hans-Joachim , Sonnenburg Christel , Stolte Hilmar
Published: November 2008

In order to decide whether foot process abnormalities in nephrotic states are the cause or the consequence of proteinuria, the polycation protamine has been applied to isolated perfused rat kidneys and functional parameters and morphology have been compared. With 110 μg/ml protamine the albumin clearance ratio increased from 2.0 + 0.7 × 10-3 in controls to 14.8 + 6.9 × 10-3 10-20 min after application and even to 98.0 + 30.8 × 10-3 after 50-80 min. Micropuncture samples collected from early proximal tubules with pressure control were used to calculate the sieving coefficient which correlated with albumin clearance ratios (controls: 1.8 +1.0 × 10-3; after 10-20min: 11.8 ± 6.4 × 10-3; after 50-80 min: 52.0 + 8.5 × 10-3). Glomerular filtration rate decreased in the early beginning from 1.1 ± 0.2 ml x min-1 ×g-1 kidney to 0.7+ 0.2 ml × min-1 ×g-1 kidney, but remained constant throughout the whole experiment. Despite the markedly increased albuminuria there were no changes in glomerular foot process morphology with the protamine dose used.
In vitro Phosphorylation of Rat Kidney Proximal Tubular Brush Border Membranes
Authors: Biber Jürg , Scalera Vito , Murer Heini
Published: November 2008

The phosphorylation of rat renal brush border membrane protein was analyzed after incubation of cortical slices with 32P-orthophosphate and compared with the phosphorylation by γ-32P-ATP of isolated brush border vesicles. Phosphate incorporation into brush border membranes isolated from slices was linearly related to the incubation time as well as to the specific activity of orthophosphate present during slice incubation. Incorporation of phosphate into proteins reached an equilibrium after about 60min, whereas incorporation of phosphate into lipids increased continuously. In brush border membranes isolated from slices incubated with orthophosphate (32P), the addition of cAMP or theophylline produced a dephosphorylation of a 47,000-dalton protein; no increased phosphorylation was observed. In brush border membranes, phosphorylated with γ-32P-ATP, cAMP and dibutyryl cAMP (dB-cAMP) produced an increase in phosphorylation but no dephosphorylation. Sodium-dependent phosphate transport in brush border membranes was not altered by an incubation of slices with cAMP or dB-cAMP. These observations suggest that the phosphorylation machinery of isolated rat renal brush border membranes does not correspond with the mechanisms leading to phosphate incorporation into brush border membrane proteins in the intact cell.
Correlation between Distal Nephron Enzyme Activity, Structure and Function in Rats during Lithium and Lithium plus Neuroleptic Treatment
Authors: Nørgaard T. , Faarup P. , Hansen B.B. , Kristensen A.R. , Christensen S.
Published: November 2008

The histochemical activities of nonspecific acid and alkaline phosphatases, NADH- and NADPH-tetrazolium reductases, α-glycerophosphate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated in kidneys from rats treated with lithium and lithium plus neuroleptics. During the first 8 weeks of lithium treatment the activity of NADH-tetrazolium reductase, succinate dehydrogenase and α-glycerophosphate dehydrogenase activity in the collecting ducts increased. The other enzymes did not change. After 8 weeks of treatment no further changes in enzyme activity occurred. Withdrawal of lithium caused normalization of enzyme activity after 8 weeks. A decrease in concentration ability was found in parallel with the increase in enzyme activities (p < 0.001). The changes in enzyme activity were not significantly correlated to morphological changes in the collecting ducts. Treatment with neuroleptics alone caused no change in enzyme activity. During combined lithium plus neuroleptic treatment the enzyme activities changed in a similar way as during lithium therapy, but the changes were less pronounced. In parallel, a less pronounced decrease in concentration ability was found during this treatment.
Urea Synthesis in the Canine Kidney
Authors: Von Dreele Margaret Mullins , Banks Robert O.
Published: November 2008

The ability of the kidney to synthesize urea is of interest and some controversy. We tested the hypothesis that low plasma urea concentrations would stimulate renal urea synthesis, thereby enhancing urinary concentrating ability. We defined a ratio of specific activity of plasma/specific activity of urine (SA ratio) greater than 1.0 as indicative of de novo intrarenal urea synthesis. We studied dogs on 3 dietary regimens: (1) commercial chow ad libitum; (2) restricted rations of the same chow; (3) protein-free diet ad libitum with vitamin/mineral supplement. A significant inverse relationship between plasma urea concentration and SA ratio was seen only in the ration-restricted group, despite the fact that plasma urea concentrations in this group were highest of the three groups. In addition, dogs in this group were more likely to demonstrate renal urea synthesis than dogs in the other groups. Thus, the dog kidney is capable of de novo urea synthesis, but a reduced plasma urea concentration does not necessarily stimulate this metabolic activity. Other factors in addition to the plasma urea concentration appear to be involved in the regulation of renal urea synthesis.
The Role of Histamine H1 and H2 Receptors in the Canine Kidney
Authors: Radke Karen J. , Selkurt Ewald E. , Willis Lynn R.
Published: November 2008

The functional role of H1 and H2 receptors in mediating the effects of histamine on renal hemodynamics and tubular function was investigated in anesthetized dogs. Histamine, infused directly into the renal artery, caused decreases in renal vascular resistance and increases in total renal blood flow without significant changes in mean arterial blood pressure or glomerular filtration rate. These hemodynamic effects of histamine were inhibited by the H2-receptor antagonist, cimetidine, but not by the H1-receptor antagonist, tripelennamine. Histamine also caused increases in fractional urine flow and the fractional excretion of sodium and calcium with a concomitant decrease in urine/plasma osmolality. These tubular effects of histamine were antagonized by both tripelennamine and cimetidine. Histamine-induced increases in the fractional excretion of potassium were blocked only by tripelennamine. These results suggest that (1) both H1 and H2 receptors mediate the effects of histamine on urinary dilution and tubular reabsorption; (2) H2 receptors mediate the effects of histamine on renal hemodynamics, indicating that H2 receptors are present in the renal vasculature, and (3) H1 receptors may exist in the renal tubules.
Participation of Prostaglandin and Adrenergic Nervous System in Renin Release Induced by Changes in Renal Arterial Pressure in Rats
Authors: Imagawa J. , Miyauchi T. , Satoh S.
Published: November 2008

The response of plasma renin activity (PRA) to stepwise reductions in renal arterial pressure (RAP) induced by suprarenal aortic constriction (SAC) or hydralazine (0.1–30 mg/kg i.v.), and the effect of indomethacin (5 mg/kg i.v.) or propranolol (1.5 mg/kg s.c.) on the PRA response were examined in anesthetized rats whose right kidneys had been removed 6–7 days earlier. The stepwise reduction of RAP by SAC or hydralazine produced a steep increase in PRA when RAP was below approximately 100 mmHg. Above this level, PRA was unaffected by changes in RAP. The SAC-induced increase in PRA was nearly abolished by indomethacin. On the other hand, propranolol failed to affect the SAC-induced increase in PRA. The hydralazine-induced renin release was remarkably suppressed by either indomethacin or propranolol. These results suggest that SAC-induced renin release is mainly dependent on the prostaglandin system, whereas hydralazine-induced renin release is dependent on the prostaglandin and the adrenergic nervous system. We estimated the threshold pressure for increasing renin release is approximately 100 mm Hg.
Beneficial Effects of Long-Term Prostaglandin E2 Infusion on the Course of Postischemic Acute Renal Failure
Authors: Neumayer H.-H. , Wagner K. , Groll J. , Schudrowitsch L. , Schultze G. , Molzahn M.
Published: November 2008

The effect of a continuous intra-aortal infusion of prostaglandin E2 (PGE2) (0.03 µg· min-1 • kg-1) on the course of postischemic renal failure (180 min cessation of blood flow by inflation of a pneumatic cuff) has been investigated in 11 conscious sodium-replete dogs. The glomerular filtration rate (51Cr-EDTA; endogenous creatinine clearance) was less decreased in the PGE2 group (group B, n = 6) than in the control group (group A, n = 5; 13 ml·min-1 vs. 22 ml min-1; p < 0.05). Renal blood flow (electromagnetic flow probe) was markedly lower in the control group (82 ml •min-1) than in the PGE2 group (130 ml • min-1; p < 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+ 277%) was abolished in the PGE2 group (-20%) (ρ < 0.05). Nitrogen retention was also markedly improved. Plasma renin activity, which was markedly raised initially (25.8 ng angiotensin I·ml-1 h-1) was not significantly further increased during the subsequent 7 days. Urinary excretion of PGE2 was diminished in the control group and elevated following PGE2 infusion. It is suggested that the beneficial effects of PGE2 are mediated by preservation of renal perfusion. Additional effects of prostanoids on the ultrafiltration coefficient (KF) and cytoprotection by reduction of intracellular calcium accumulation must also be taken into consideration.
Interaction between Laminin, Fibronectin and the Light Chain of the H2 Complex
Authors: Lubec Gert
Published: November 2008

At present the detailed mechanism for transmembrane interactions is not known and a protein linked to the endoskeleton as well as to the exoskeleton has not been described as yet. The H2 complex, a transmembrane protein, consists of heavy and light chains, the latter is named beta-2-microglobulin. In order to look for an association of beta-2-microglobulin with an exoskeleton protein, we examined the extracellular matrix proteins, collagen type I, type IV, fibronectin, amyloid P, the solubilized glomerular basement membrane and lamiriin in respect to their interaction with the light chain. The heavy chain is known to bind strongly to the endoskeleton protein actin. Only laminin and the glomerular basement membrane bound firmly to the beta-2-microglobulin; 3 M urea was necessary to dissociate the formed complex. Incubation with beta-2-microglobulin antibody prevented binding of beta-2-microglobulin to laminin and the glomerular basement membrane on affinity chromatography columns. Antiserum to the glomerular basement membrane in turn prevented binding of beta-2-microglobulin to the glomerular basement membrane, whereas antibodies against the basement membrane collagen type IV failed to inhibit this binding to the glomerular basement membrane. Beta-2-microglobulin also bound to ñbronectin but this complex was dissociated with 1 M urea. In a rosette assay beta-2-microglobulin antibody and antiserum to the glomerular basement membrane reduced attachment of glomerular cells to beads coupled with laminin and solubilized glomerular cells to beads coupled with laminin and solubilized glomerular basement membrane. Also antibody against fibronectin reduced attachment of glomerular cells to fibronectin-coated beads. In an organ reconstruction assay, glomerular cells showed reduced binding to the glomerular scaffold if antibodies to the solubilized glomerular basement membrane or fibronectin were applied, but not if anti-type-IV collagen antibodies were used. This points to the role of laminin and fibronectin for the attachment to glomerular cells, where the receptor could be identified as beta-2-microglobulin, the light chain of the H2 complex, thus linking the endoskeleton with the exoskeleton. Only differences in the binding affinities between laminin and fibronectin were detected.
Epithelial Cell Volume Regulation Illustrated by Experiments in Frog Skin
Authors: Ussing Hans H.
Published: November 2008

The volume control of the syncytium of principal cells (as opposed to the mitochondria-rich cells) is largely confined to the movement of ions and water through the basolateral membrane. The apical membrane is nearly tight to water and ions except sodium. The basolateral membrane is normally tight to chloride, but its chloride channels open if the cells swell osmotically or if the membrane is depolarized. If the epithelium has lost KC1 during osmotic swelling, it is recovered by a basolateral cotransport of KNaCl2
Urinary Kinin Excretion Following Alterations of Vasopressin Levels in Man and Rat
Authors: Náray-Fejes-Tóth Anikó , Fejes-Tóth Géza
Published: November 2008

To investigate the interaction between arginine-vasopressin (AVP) and the renal kallikrein-kinin system (KKS), urinary excretion rates of bradykinin (BK) and lysyl-brady-kinin (LBK) were monitored in humans following water-loading, and in conscious diabetes insipidus (DI) rats during the infusion of AVP. In humans, the excretion rate of both BK and LBK decreased markedly 90 min after the water load. There was a close positive correlation between plasma AVP levels and urinary BK excretion, while urine flow was correlated negatively with the excretion rates of both kinins. In DI rats infusion of AVP caused a significant, reversible increase (from 14 ± 2.8 to 35 ± 5.1 fmol/min) in BK excretion. These results further implicate AVP in the regulation of the activity of the renal KKS.
Acute Effect of Cisplatin on Renal Hemodynamics and Tubular Function in Dog Kidneys
Authors: Daugaard Gedske , Abildgaard Ulrik , Holstein-Rathlou Niels-Henrik , Leyssac Paul P. , Amtorp Ole , Dikhoff Theo G.
Published: November 2008

The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and significant increase in urinary flow rate (from 0.39 ± 0.07ml/min to 0.73 ± 0.12ml/min), sodium clearance (from 0.33 ± 0.11 ml/min to 0.65 ± 0.14ml/min), potassium clearance (from 9.23 ± 0.48ml/min to 10.77 ± 0.95 ml/min), lithium clearance (from 15.55 ± 2.21 ml/min to 23.76 ± 4.00ml/min) and fractional lithium clearance (from 0.31 ± 0.03 to 0.44 ± 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 ± 0.03 to 0.56 ± 0.04 and from 4.76 ± 0.32mmol/min to 3.92 ± 0.23mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics.
Single Nephron Hyperfiltration and Proteinuria in a Newly Selected Rat Strain with Superficial Glomeruli
Authors: Rovira-Halbach G. , Alt J.M. , Brunkhorst R. , Frei U. , Kühn K. , Stolte H.
Published: November 2008

Alterations in glomerular permeability were studied in female MWF/Ztm rats, newly selected from the Munich Wistar rats with a high number of superficial glomeruli. This strain is characterized by a diminished number of functioning nephrons, an elevated arterial blood pressure and a high proteinuria averaging 24 mg/24 h. Samples of Bowman capsular space (BCS) obtained by free-flow renal micropuncture techniques with pressure control were analyzed for albumin and high-molecular-weight (HMW) proteins by ultramicrodisc electrophoresis. The measured mean albumin and HMW protein concentration in BCS were 1.72 g/l and 0.66 g/l, respectively. The glomerular filtration rate (GFR) averaged 0.74 ml/min/g kidney weight and the single nephron GFR (SNGFR) 48 nl/min. Ultrastructural studies revealed focal bleb-like alterations of the podocytes as has been observed in hyperfîltration states. We suggest that the reduced number of functioning nephrons in the kidneys of these rats could induce glomerular hyperfiltration and permselectivity changes, which cause a high glomerular protein leakage.
Angiotensin II: Preferential Efferent Constriction?
Authors: Heller Jiři , Horáčcek Vladislav
Published: November 2008

In dogs with maximal subpression of endogenous angiotensin II (All) production due to a high-salt diet and converting enzyme inhibition (CEI, SQ 14,225, 15 µg · kg-1 · min-1 i.v.), infusion of a subpressor dose of angiotensin II (1 ng · kg-1 · min-1) did not change contralateral kidney function. In the infused kidney, a decrease in renal blood flow (RBF) by 24% and glomerular filtration rate (GFR) by 9% with an increase in filtration fraction (FF) by 20% occurred. Similarly, the increase in single nephron (SN) RBF was greater than in SNGFR, thus rising SNFF by 8%. Glomerular capillary pressure (GCP) did not change significantly; a decrease by 20% in proximal tubule pressure thus resulted in an increase in △HP by 22%. This increase counterbalanced the profound drop in ultrafiltration coefficient (Kf) (57%) making the decrease in GFR and SNGFR relatively small. Total arteriolar resistance (Rj) rose by 26%, the rise being due mainly to an increase in efferent (RE, 50%) rather than afferent (RA, 4%) resistance. If the All infusion was carried out during concomitant infusion of CEI and indomethacin (1 mg · kg-1 · min-1) or aspirin (5 mg · kg-1 · min-1), RBF decreased by 36%, GFR by 25%, thus increasing FF by 18%; corresponding SN values underwent similar changes. Drop in Kf amounted to 62% and hydraulic pressure difference (△HP) increased by 11% with unchanged GCP. The increase in Rτ (72%) was now due to a very similar increase in both RA (68%) and Re (76%). In conclusion, a very small dose of All exhibits – at least in superficial nephrons – a typical preferential efferent effect which disappears after inhibition of prostanoid synthesis, indicating a protective effect of vasodilatory prostaglandins mainly on the afferent arteriole.
Effect of Erythrocytes on the Function and Morphology of the Isolated Perfused Rat Kidney
Authors: Lieberthal Wilfred , Stephens Gregory W. , Wolf Eileen F. , Rennke Helmut G. , Vasilevsky Murray L. , Valeri Robert , Levinsky Norman G.
Published: November 2008

We have examined the effects of erythrocytes on the function and morphology of isolated rat kidneys perfused with a physiological concentration of bovine albumin (45 g/l). (1) In kidneys perfused without red cells, renal vascular resistance (RVR) was low (4.2 ± 0.3 mm Hg/ml/min/g), fractional sodium excretion (FeNa) was high (14.5 ± 1.8%) and concentrating ability impaired (maximum urine osmolality 343 ± 4 mmol/kg). The erythrocyte-free kidney also developed necrosis of the cells of the medullary thick ascending limb (mTAL). (2) Erythrocytes at a hematocrit of 4–6% did not alter RVR but prevented ischemic changes in the mTAL and reduced FeNa to 9.4 ± 0.03%. Concentrating ability was not improved by a hematocrit of 4–6% despite the presence of a morphologically normal mTAL. (3) At a hematocrit of 40–45%, RVR was increased (to 11.2 ± 0.4 mm Hg/ml/min/g) and FeNa was further lowered to 3.5 ± 0.6%. Also, urinary concentrating ability was markedly improved (maximum urine osmolality 640 ± 35 mmol/kg). (4) The isolated perfused kidney (IPK) at a hematocrit of 40–45% was able to autoregulate renal perfusate flow rate of GFR but auto-regulation was incomplete. A 50% increase in perfusion pressure from 100 to 150 mm Hg increased renal perfusate flow rate and GFR 27 and 29%, respectively. Thus the IPK is not able to autoregulete as efficiently as the kidney in vivo, even in the presence of red cells at a normal hematocrit.
Participation of the Prostaglandin System in Furosemide-Induced Changes of Renal Function in Anesthetized Rats
Authors: Yoshida M. , Suzuki-Kusaba M. , Satoh S.
Published: November 2008

The possible mediation of the endogenous prostaglandin and kallikrein-kinin systems of changes in renal function induced by furosemide was studied in anesthetized rats. Increasing doses of furosemide infusion (0.03, 0.1, and 0.3 mg/kg/min) caused dose-related diuresis, natriuresis, kaliuresis, and decreased renal blood flow and urinary osmolality without any significant changes in mean arterial blood pressure. Pretreatment with the prostaglandin synthetase inhibitor indomethacin resulted in marked reduction of the water and sodium excretion induced by furosemide. It also blunted renal vasoconstriction and renin release by furosemide, but the glomerular filtration rate was not affected. Pretreatment with aprotinin, a kallikrein inhibitor, failed to affect the renal response to furosemide. The results indicate that the renal prostaglandin system, but not the kallikrein-kinin system, participates in the effect of furosemide on renal functions mainly through electrolyte transport inhibition in the renal tubule.
Intranephron Distribution of Epidermal Growth Factor Immunoreactivity in the Mouse
Authors: Oka Yuji , Fujiwara Kenji , Endou° Hitoshi
Published: November 2008

Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, the distribution of EGF in mouse kidneys was studied. In five portions (outer cortex, inner cortex, outer medulla I, II, and papilla) of kidney slices, the outer medulla revealed the highest immunoreactive EGF (iEGF) per wet weight of tissue. In microdissected nephron segments, the predominant iEGF per millimeter length was observed in the medullary and cortical thick ascending limbs of Henle’s loop compared with other segments. It became more apparent when expressed per milligram protein. Fluorescence microscopy showed prominent staining for EGF in the thick ascending limbs of Henle’s loop. The significance of the nephron heterogeneity in EGF contents is discussed.
Outflow Segment of the Efferent Arteriole of the Rat Glomerulus Investigated by in vivo and Electron Microscopy
Authors: Schnabel E. , Kriz W. , Steinhausen M.
Published: November 2008

In previous intravital microscopic studies of the hydronephrotic split kidney a narrow segment in the efferent arteriole at its origin from the glomerulus was observed. In the present study in vivo techniques were combined with transmission electron microscopy of thin sections to investigate the structural basis for the luminal narrowing. At the point where the efferent arteriole leaves Bowman’s capsule prominent endothelial cells were found to bulge into the lumen of the vessel. These cells participate in the overall narrowing of the lumen at this site and appear to be responsible for the in vivo picture. However, the principal basis for the narrowing seems to be an extrinsic constriction of the vessel, possibly by extraglomerular mesangial cells located at the exit level. It is suggested that the outflow portion of the efferent arteriole may be an important site of control of glomerular blood flow.
Cell Volume Regulation in the Nervous System
Authors: Ballanyi K. , Grafe P.
Published: November 2008

There is good evidence that the three main compartments of the brain, i.e. extracellular space, neurones and glial cells, change their volume during physiological and pathophysiological neuronal activity. However, there is strikingly little knowledge about the mechanisms underlying such alterations in cell volume. For this purpose, a better understanding of the electrophysiological behavior of the neurones and glial cells during volume changes is necessary. Examples are discussed for which changes in cell volume can be derived from the underlying changes in membrane permeabilities. Volume regulatory mechanisms in the brain have not been described under isotonic conditions. However, a rapid volume regulatory decrease is occurring in cultured glial cells during exposure to hypotonic solutions. In contrast, in these cells no volume regulatory increase was found during superfusion with hypertonic media. On the other hand, the entire brain is able to compensate chronic hypertonic perturbations within hours to days. Interestingly, not only ion fluxes induce cellular volume changes but, in turn, water movements can also influence ion fluxes in both neurones and glial cells. With respect to this it should be considered that volume regulatory membrane processes might not exclusively be activated by changes in transmembranal ion gradients, but also by changes of membrane surface shape. Future studies on cellular mechanisms of volume regulation in the brain should imply a combined use of recent techniques such as computerized video-imaging, radiotracer flux measurements and ion-sensitive microelectrodes in defined cell cultures. Optical monitoring and ion-sensitive microelectrodes should enable measurements of volume changes in identified cellular elements of intact nervous structures such as brain slices.
Cell Volume Regulation in Renal Cortical Cells
Authors: Völkl H. , Paulmichl M. , Lang F.
Published: November 2008

Both proximal renal tubule cells and cultured Madin-Darby canine kidney (MDCK) cells are capable of regulating their volume in hypotonic media. Regulatory cell volume decrease in proximal straight tubules is impaired by barium, amiloride and acetazolamide and depends on the presence of bicarbonate and of sodium, whereas it is unaffected by complete removal of extracellular chloride. The observations may point to parallel loss of potassium through potassium channels as well as of bicarbonate and sodium via a bicarbonate-sodium cotransport. Alternatively, potassium/hydrogen ion exchange or potassium bicarbonate cotransport could be involved. In MDCK cells, exposure to hypotonic media apparently leads to the activation of an anion channel, while potassium conductance is rather decreased. In both proximal tubules and MDCK cells, volume regulatory decrease is possibly triggered by leucotrienes, which may be released during cell swelling. Cell volume is altered in a variety of conditions even at isotonic extracellular fluid and cell volume-regulatory mechanisms are likely to participate in regulation of renal transepithelial transport.
Hemodynamic Interactions between Intrinsic Blood Flow Control Mechanisms in the Rat Kidney
Authors: Häberle D.A.
Published: November 2008

In order to reconcile the controversial concepts of myogenically and tubuloglomerular-feedback (TGF)-mediated control of renal vascular resistance, a hypothesis is advanced according to which both mechanisms interact hemodynamically because of their serial arrangement. Whereas the myogenic mechanism is suggested to be localized in the more upstream segments of the preglomerular resistance vessels, the TGF mechanism is assumed to control the pre- and/or postglomerular vascular segment(s), close to the glomerular vascular pole. The efferent vascular resistance, however, is assumed to function generally akin to a ‘passive’ flow resistor. These assumptions together with elementary hemodynamic considerations, allow formulation of a simple renal hemodynamic model whose quantitative predications regarding the characteristics of RBF, GFR and TGF control are remarkably consistent with the literature: (1) the magnitude of TGF response is mainly dependent upon the myogenic cooperative amplification and (2) although the TGF mechanism is not involved in the auto-regulative control of RBF and GFR, changes of the TGF function may shift the autoregulation curve to higher or lower RBF and blood pressure levels.
A New Method for Collecting Urine Directly from the Ureter in Conscious Unrestrained Rats
Authors: Horst Peter-Joachim , Bauer Martin , Veelken Roland , Unger Thomas
Published: November 2008

We have developed a new method for urine collection in conscious, unrestrained rats through a chronic indwelling ureteral catheter, which allows direct differential sampling of small urine fractions over periods as small as 1 min. The technique was validated in intact and unilaterally nephrectomized rats by cumulative intravenous saline loading. Comparison of kidney with ureter catheter and contralateral kidney (urine collection from the bladder) revealed no differences in glomerular filtration rate and urine production between both kidneys. One week after catheter implantation in unilaterally nephrectomized rats, signs of renal functional disturbance as assessed by glomerular filtration rate, urine concentrating capacity after 24 h water deprivation, and plasma and urinary urea concentrations before and after water deprivation were not detected. Our technique provides a novel tool for direct measurements of short-term changes in urine composition in conscious animals.
Microcomputer Simulation as an Aid in Analyzing Data and Teaching the Principles of Glomerular Dynamics
Authors: Oken Donald E.
Published: November 2008

This report describes a simple program, written in BASIC language, that closely emulates a previously published network thermodynamic model of glomerular dynamics. While the latter requires the SPICE 2 simulation program and a mainframe computer for its execution, the present program operates on any IBM®-compatible microcomputer. It has equal utility as an aid in the interpretation of laboratory studies of glomerular dynamics and as a tool for teaching the intricacies of the control of glomerular function. The program is available in ‘user friendly’ format that obviates the need for any expertise in the use of computers.
Farp2
and
Stk25
Are Candidate Genes for the HDL Cholesterol Locus on Mouse Chromosome 1
Authors: Su Zhiguang , Cox Allison , Shen Yuan , Stylianou Ioannis M. , Paigen Beverly
Published: November 2008

Objective—

To identify the gene responsible for the quantitative trait locus (QTL)
Hdlq14
, a high-density lipoprotein cholesterol (HDL) QTL previously identified in a C57BL/6J×129S1/SvImJ cross.

Methods and Results—

Hdlq14
was first confirmed as an independent QTL by detecting it in an intercross between NZB/B1NJ and NZW/LacJ, 2 strains that had identical genotypes at nearby QTL genes on chromosome 1. Using the bioinformatics tools of combined cross data and haplotype analysis, we narrowed this QTL from a 45-Mb 225-gene region to 2 genes,
Farp2
and
Stk25
. Sequencing and expression studies showed that
Farp2
had an amino acid polymorphism in an important plekstrin domain and that
Stk25
had a significant expression difference between the parental strains. These 2 genes are immediately adjacent to each other and share the same haplotype over 45 inbred strains. The haplotype was associated with a significant difference in HDL levels among these strains.

Conclusion—

We confirmed
Hdlq14
as a separate independent QTL for HDL and narrowed the region to 2 genes,
Farp2
and
Stk25
, with considerable evidence for both. Additional studies are needed to choose between these 2 genes or to show that both are important in determining HDL levels.
O
-Linked GlcNAc Modification of Cardiac Myofilament Proteins
Authors: Ramirez-Correa Genaro A. , Jin Wenhai , Wang Zihao , Zhong Xin , Gao Wei Dong , Dias Wagner B. , Vecoli Cecilia , Hart Gerald W. , Murphy Anne M.
Published: November 2008

In addition to
O
-phosphorylation,
O
-linked modifications of serine and threonine by β-
N
-acetyl-
d
-glucosamine (GlcNAc) may regulate muscle contractile function. This study assessed the potential role of
O
-GlcNAcylation in cardiac muscle contractile activation. To identify specific sites of
O
-GlcNAcylation in cardiac myofilament proteins, a recently developed methodology based on GalNAz-biotin labeling followed by dithiothreitol replacement and light chromatography/tandem mass spectrometry site mapping was adopted. Thirty-two
O
-GlcNAcylated peptides from cardiac myofilaments were identified on cardiac myosin heavy chain, actin, myosin light chains, and troponin I. To assess the potential physiological role of the GlcNAc, force–[Ca
2+
] relationships were studied in skinned rat trabeculae. Exposure to GlcNAc significantly decreased calcium sensitivity (pCa50), whereas maximal force (
F
max
) and Hill coefficient (
n
) were not modified. Using a pan-specific
O
-GlcNAc antibody, it was determined that acute exposure of myofilaments to GlcNAc induced a significant increase in actin
O
-GlcNAcylation. This study provides the first identification of
O
-GlcNAcylation sites in cardiac myofilament proteins and demonstrates their potential role in regulating myocardial contractile function.
DWI Lesions and TIA Etiology Improve the Prediction of Stroke After TIA
Authors: Calvet David , Touzé Emmanuel , Oppenheim Catherine , Turc Guillaume , Meder Jean-François , Mas Jean-Louis
Published: November 2008

Background and Purpose—

The ABCD
2
score has been shown to predict the early risk of stroke after transient ischemic attack (TIA). The additional predictive value of diffusion-weighted imaging (DWI) and TIA etiology is not well known.

Methods—

From January 2003 to June 2007, 343 consecutive patients (mean±SD age, 62.4±15.4 years) with TIA were admitted to our stroke unit. Most (339) patients underwent DWI and all had an etiologic work-up and were followed up for 3 months. The predictive value of the ABCD
2
score, positive DWI findings, large-artery atherosclerosis (LAA), and atrial fibrillation (AF) with respect to occurrence of ischemic stroke at 1 week and 3 months was assessed.

Results—

DWI was positive in 136 (40%) patients. Sixty (17%) patients had LAA and 27 (8%) had AF. Patients with positive DWI findings were more likely to have unilateral weakness (odds ratio [OR]=2.2; 95% CI, 1.3 to 3.7), TIA duration ≥60 minutes (OR=2.6; 95% CI, 1.3 to 5.2), ABCD
2
>5 (OR=4.7; 95% CI, 2.0 to 11.0), LAA (OR=1.8; 95% CI, 1.0 to 3.1), and AF (OR=3.5; 95% CI, 1.5 to 8.0). During follow-up, 5 patients had a stroke within 7 days (absolute risk=1.5%, 95% CI, 0.3% to 2.7%), and 10 had a stroke within 3 months (absolute risk=2.9%; 95% CI, 1.1% to 4.7%). All early strokes but 1 occurred in patients with positive DWI findings. ABCD
2
score and positive DWI findings were associated with an increased 7-day and 3-month risk of stroke. At 3 months, ABCD
2
score >5 (hazard ratio=10.1; 95% CI, 1.1 to 93.4), positive DWI result (hazard ratio=8.7; 95% CI, 1.1 to 71.0), and LAA (hazard ratio=3.4; 95% CI, 1.0 to 11.8) were independently associated with an increased risk of stroke. There was no association with AF.

Conclusions—

Taking DWI and TIA etiology into account in addition to the ABCD
2
score improves the prediction of the early risk of stroke after TIA.
Pathomechanisms of Symptomatic Developmental Venous Anomalies
Authors: Pereira Vitor M. , Geibprasert Sasikhan , Krings Timo , Aurboonyawat Thaweesak , Ozanne Augustin , Toulgoat Frederique , Pongpech Sirintara , Lasjaunias Pierre L.
Published: November 2008

Background and Purpose—Although it is generally accepted that developmental venous anomalies (DVAs) are benign vascular malformations, over the past years, we have seen patients with symptomatic DVAs. Therefore, we performed a retrospective study and a literature study to review how, when, and why DVAs can become clinically significant.

Methods—Charts and angiographic films of 17 patients with DVAs whose 18 vascular symptoms could be attributed to a DVA were selected from a neurovascular databank of our hospital. MRI had to be available to rule out any other associated disease. In the literature, 51 cases of well-documented symptomatic DVAs were found. Pathomechanisms were divided into mechanical and flow-related causes.

Results—Mechanical (obstructive or compressive) pathomechanisms accounted for 14 of 69 symptomatic patients resulting in hydrocephalus or nerve compression syndromes. Flow-related pathomechanisms (49 of 69 patients) could be subdivided into complications resulting from an increase of flow into the DVA (owing to an arteriovenous shunt using the DVA as the drainage route; n=19) or a decrease of outflow (n=26) or a remote shunt with increased venous pressure (n=4) leading to symptoms of venous congestion. In 6 cases, no specific pathomechanisms were detected.

Conclusions—Although DVAs should be considered benign, under rare circumstances, they can be symptomatic. DVAs, as extreme variations of normal venous drainage, may represent a more fragile venous drainage system that can be more easily affected by in- and outflow alterations. The integrity of the DVA needs to be preserved irrespective of the treatment that should be tailored to the specific pathomechanism.