bluuebunny/crossref_metadata_2025 huggingface dataset:
Urea flux in the ureter
Authors: Walser B. L. , Yagil Y. , Jamison R. L.
Published: December 2017

It has been hypothesized that urea from the final urine is recycled into the renal papilla through the pelvic epithelium. To test this hypothesis, samples of urine were collected by micropuncture proximally and distally through the intact, contracting ureter of the anesthetized rat. In 12 rats, in which urine flow was 5.89 +/- 0.67 microliter/min (a moderate antidiuresis), the ratio of proximal-to-distal urea concentration, corrected for water movement, was 0.93 +/- 0.03 (P less than 0.01 compared with unity), indicating that approximately 7% of urea in the urine emerging from the terminal collecting duct was reabsorbed by the time it reached the distal ureter. To assess the possible contribution of urea reabsorption by the ureter, the ureter was cannulated proximally and distally and perfused with urine of known composition at 6.26 +/- 0.10 microliter/min. In nine rats, the ratio of urea concentration in the perfusate collected from the distal end of the ureter to that in the perfusate entering the proximal end was 0.93 +/- 0.02 (P less than 0.01 compared with unity), indicating 7% reabsorption. Movement of solute across the ureteral epithelium was not restricted to urea. Potassium and creatinine were also reabsorbed [3.4 +/- 0.9 (P less than 0.01) and 3.5 +/- 1.2% (P less than 0.05), respectively], whereas sodium was secreted [9.2 +/- 2.3% (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)
Amino acid transport by juxtamedullary nephrons: distal reabsorption and recycling
Authors: Dantzler W. H. , Silbernagl S.
Published: December 2017

Amino acid transport by juxtamedullary (JM) nephrons and its relationship to transport by superficial cortical (SC) nephrons and to function of vasa recta and collecting ducts were examined in vivo and in situ by free-flow micropuncture of Henle's loops, collecting ducts, and vasa recta and by continuous microinfusion of Henle's loops in exposed rat papillae. Fractional deliveries (FDs) of six neutral amino acids, two acidic amino acids, and taurine to tips of Henle's loops of JM nephrons could be substantially below those to early distal loops of SC nephrons, indicating that reabsorption before loop tips could be greater in JM than in SC nephrons. FDs to collecting ducts lower than to JM loop tips suggested reabsorption distal to loop tips. This was confirmed by continuous microinfusion of ascending limbs of Henle's loops. Distal site of reabsorption is unknown, but amino acids may move passively out of the thin ascending limb and be recycled into vasa recta and descending limb. Recycling of amino acids was supported by high FDs to tips of Henle's loops (sometimes greater than 1.0), higher concentrations in ascending than in descending vasa recta at same papilla level, and high mean concentrations in vasa recta.
Neutrophils accentuate ischemia-reperfusion injury in isolated perfused rat kidneys
Authors: Linas S. L. , Shanley P. F. , Whittenburg D. , Berger E. , Repine J. E.
Published: December 2017

The contribution of neutrophils to reperfusion injury after ischemia is not known. To determine the effect of neutrophils on the function of ischemic kidneys, we added purified human neutrophils during perfusion of isolated ischemic or nonischemic rat kidneys. Reperfusion of ischemic kidneys with neutrophils caused a distinct morphological lesion of vascular endothelial and smooth muscle cells and more functional injury than reperfusion with buffered albumin alone; with neutrophils, glomerular filtration rate (GFR) was 113 +/- 7 microliter.min-1.g-1, tubular sodium reabsorption (TNa) was 72 +/- 2%; without neutrophils, GFR was 222 +/- 18 microliter.min-1.g-1; TNa was 90 +/- 2%; both P less than 0.01 vs. reperfusion with neutrophils. In contrast, addition of neutrophils did not injure control kidneys, unless the neutrophil activator, phorbol myristate acetate, was also added. Two experiments suggested that O2 metabolites contributed to neutrophil-mediated injury to ischemic kidneys. First, reperfusion of ischemic kidneys with O2 metabolite-deficient neutrophils from a patient with chronic granulomatous disease did not cause more injury than reperfusion with buffered albumin alone. Second, simultaneous addition of the O2 metabolite scavenger, catalase, prevented the GFR and TNa decreases caused by neutrophils but did not decrease injury in the absence of neutrophils. We conclude that neutrophils by an O2 metabolite-dependent mechanism contribute to ischemia-reperfusion injury in the isolated perfused kidney.
AVP-sensitive cAMP production is dependent on calmodulin in both MTAL and MCT
Authors: Takaichi K. , Kurokawa K.
Published: December 2017

Vasopressin (AVP) plays a key role in maximal urine concentration by stimulating NaCl reabsorption in the medullary thick ascending limbs of Henle (MTAL) and by increasing water permeability in the medullary collecting tubules (MCT). These effects of AVP in MTAL and MCT are mediated by activation of adenylate cyclase. Because effects of high ambient Ca2+ on AVP-sensitive adenosine 3',5'-cyclic monophosphate (cAMP) production are quite different in MTAL and MCT, we examined whether the Ca2+-calmodulin system is involved differently in AVP-sensitive cAMP production in MTAL and MCT of mouse kidney using two dissimilar calmodulin inhibitors, trifluoperazine (TFP) and W-7. TFP and W-7 inhibited AVP-sensitive cAMP production in both nephron segments in a dose-dependent manner with maximal inhibition of both agents being greater than 90%. A half-maximal inhibition by TFP and W-7 was about 45, 100 microM in MTAL and about 40, 40 microM in MCT, respectively. The inhibitory effect of W-5, a chemically similar to W-7 but less potent calmodulin inhibitor, was significantly less than that of W-7 in both nephron segments. TFP and W-7 but not W-5 also inhibited glucagon-sensitive cAMP production in MTAL. W-7 inhibited forskolin-sensitive cAMP production but the inhibition by W-5 was significantly less than that by W-7 in MTAL and MCT. Results suggest that AVP-sensitive cAMP production is MCT.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of a physiological dose of ANP on renal function in dogs
Authors: Banks R. O.
Published: December 2017

The current study was designed to evaluate the effects of a physiological dose (1.0 ng.kg-1.min-1 into the renal artery) of atrial natriuretic peptide (ANP, 8-33) on renal function in anesthetized mongrel dogs. Left renal blood flow (RBF) was measured with a flow probe and the glomerular filtration rate (GFR) using both clearance and renal extraction methodologies. After a 60- to 90-min stabilization period and collection of two 5-min control clearances, ANP was infused for 20 min, with four 5-min clearances performed. The increase in ANP concentration in renal arterial plasma (calculated from the ANP infusion rate and the renal plasma flow) was 212 +/- 9 (SE) pg/ml. During each experimental period there was a saliuresis and diuresis, an increase in the reabsorption of solute-free water, and an increase in the creatinine clearance; mean arterial blood pressure and the GFR, calculated from extaction data, were unaffected by ANP.RBF was 3.28 +/- 0.21 during control and 3.03 +/- 0.22 ml.min-1.g-1 at 20 min during ANP infusion (P less than 0.01). These data demonstrate that a physiological dose of ANP is natriuretic and diuretic, causes a modest decrease in RBF without affecting the GFR, and causes a condition in which clearance methods can overestimate the GFR.
Mechanism of Li inhibition of vasopressin-sensitive adenylate cyclase in cultured renal epithelial cells
Authors: Goldberg H. , Clayman P. , Skorecki K.
Published: December 2017

We investigated the mechanism for lithium-induced inhibition of vasopressin-stimulated adensoine 3',5'-cyclic monophosphate (cAMP) production in the renal epithelial cell line LLC-PK1. In LLC-PK1 membranes lithium caused direct inhibition of hormone-stimulated adenylate cyclase activity by competing with magnesium. Fifty percent inhibition occurred at 20 mM lithium. The maximum transport activity (Vmax) but not the activation constant (Ka) for activation by vasopressin was altered. Activation by GTP and its nonhydrolyzable analogues was also inhibited by lithium. Furthermore, kinetic studies revealed that the lag phase in the activation of adenylate cyclase by 5'-guanylimi-dotriphosphate [Gpp(NH)p] was prolonged from 1 to 3 min, suggesting an effect of lithium on magnesium-dependent activation of the stimulatory GTP binding protein Gs. The function of the corresponding inhibitory GTP-binding protein Gi, as assessed by GTP inhibition of vasopressin-stimulated adenylate cyclase activity in the presence and absence of pertussis toxin pretreatment, was unaffected. Intact LLC-PK1 cells incubated in 10 mM lithium (approximate urinary concentration in lithium-treated patients) attained an intracellular lithium concentration of 17 mM, which led to a 40% reduction in cAMP formation. Magnesium loading of intact cells with the ionophore A23187 reversed the inhibitory effect of lithium. It is concluded that lithium directly inhibits the activation of vasopressin-sensitive adenylate cyclase in renal epithelia by competing with magnesium for activation of Gs. This direct effect on Gs activation accounts for the inhibitory effect of lithium on cAMP production in the intact cell.
Endogenous ANP augments fractional excretion of Pi, Ca, and Na in rats with reduced renal mass
Authors: Ortola F. V. , Ballermann B. J. , Brenner B. M.
Published: December 2017

Atrial natriuretic peptide (ANP) infusion increases fractional excretion of many solutes including sodium, chloride, bicarbonate, phosphate, calcium, and magnesium. Because fractional excretion of these solutes increases with advancing renal disease, and because plasma ANP levels are known to be elevated in chronic renal failure, we sought to determine whether ANP mediates increased solute excretion rates per nephron in rats following extensive renal ablation, a model of chronic renal failure. Because sodium restriction decreases plasma ANP levels in the setting of reduced renal mass, we also determined the effect of sodium restriction on sodium, phosphate, calcium, and magnesium excretion rates in rats with 5/6 nephrectomy (NX). We also assessed whether high endogenous ANP levels influence fractional sodium, phosphate, calcium, and magnesium excretion in rats with 5/6 NX, by inhibiting ANP action via infusion of a high-affinity ANP antiserum. Whole-kidney glomerular filtration rate in 5/6 NX rats averaged approximately one-third that of shams, and plasma ANP levels were significantly elevated in these rats above those of shams, but to a lesser extent in rats on low- vs. high-salt intakes. Fractional sodium, phosphate, and calcium, but not magnesium excretion rates were significantly greater in 5/6 NX rats on the higher sodium intake compared with those in 5/6 NX rats on the lower sodium intake. Moreover, in 5/6 NX rats on the higher sodium intake, ANP antiserum significantly reduced fractional sodium, phosphate, and calcium excretion, but was without effect on magnesium excretion. These data implicate endogenous ANP in promoting the adaptive increase in sodium, phosphate, calcium, but not magnesium excretion per nephron in chronic renal disease.
Contribution of purine nucleotide cycle to intranephron ammoniagenesis in rats
Authors: Tamura K. , Endou H.
Published: December 2017

To evaluate the contribution of the purine nucleotide cycle (PNC) in renal ammoniagenesis, ammonia production (AP) in cortical tubular suspensions and microdissected nephron segments of control and acidotic rats was determined using various amino acids, including glutamine (Gln) and aspartate (Asp). In the cortical tubular suspensions, the best substrate for ammoniagenesis was Gln (153.1 +/- 19.4 nmol.mg protein-1.15 min-1) followed by Asp (70.9 +/- 11.4). Metabolic acidosis resulted in a significant increase of AP only from Gln (316.5 +/- 36.1 nmol.mg protein-1.15 min-1, P less than 0.01 vs. control). Intranephron distribution of AP (pmol/mm or a glomerulus/15 min) from Gln showed that the first segment of the proximal tubule (S1) was highest in control (95.7 +/- 9.0), and its AP markedly increased in acidosis (221.6 +/- 8.3, P less than 0.001 vs. control). The most interesting and striking finding was that with Asp as a substrate, AP was maximal in S1 (165.0 +/- 32.8), with a value exceeding that from Gln. An adenylosuccinase inhibitor, 6-mercaptopurine (0.1 mM), significantly inhibited AP from Asp in S1 and S3, and from Gln in S1. On the contrary, a specific inhibitor of phosphoenolpyruvate carboxykinase, 3-mercaptopicolinate (0.1 mM), caused a significant decrease of AP from Gln, but not from Asp, in S1. From these results it could be concluded that AP via PNC can occur at high rates, especially in S1, only when Asp is present at high concentrations.
Tubular handling of neurotensin in the rat kidney as studied by micropuncture and HPLC
Authors: Bjerke T. , Christensen E. I. , Boye N.
Published: December 2017

Micropuncture studies were performed to assess the reabsorption and metabolism of the vasoactive peptide neurotensin (NT) in individual nephron segments and compare it to the handling of the closely related peptide bradykinin (BK). Rat proximal and distal convoluted tubules were microinfused with [3H]NT or [3H]BK. In a second set of experiments, [3H]NT and its metabolites in the ureteral urine were separated and characterized using high-performance liquid chromatography (HPLC) technique. The urinary recovery of 3H-labeled material was 31% when proximal tubules were microinfused with [3H]NT and 94% when distal tubules were infused. For proximal tubules the label recovered in the ureteral urine consisted exclusively of metabolites of NT and appeared as tyrosine, NT1-11, probably NT9-13, and two uncharacterized products. For distal tubules, 9% chromatographed as intact NT in the urine and except for the proportion the metabolites were almost identical to those found when proximal tubules were microinfused. Following microinfusion of [3H]BK into proximal tubules, the urinary recovery of 3H-labeled material was 19%. There was no correlation between fractional reabsorption of 3H-labeled material and proximal tubular length when [3H]NT or [3H]BK was microinfused. In vitro incubation studies with rat ureteral urine showed extensive degradation of NT yielding tyrosine, NT1-6, probably NT9-13, NT, and two uncharacterized products. In contrast, there was no detectable breakdown of BK over a 32-min period. Finally, [3H]NT was incubated in rat serum, and these experiments also showed degradation of the peptide but not to the extent as when incubated in ureteral urine.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship of GTP-binding proteins, phospholipase C, and PGE2 synthesis in rat glomerular mesangial cells
Authors: Schlondorff D. , Singhal P. , Hassid A. , Satriano J. A. , DeCandido S.
Published: December 2017

We evaluated the role of GTP-binding proteins in the activation of phospholipase C, release of arachidonic acid, and synthesis of prostaglandin (PG) E2 in response to platelet-activating factor (PAF) and angiotensin II (ANG II) in cultured rat mesangial cells. Pretreatment with pertussis toxin (PT) decreased PGE2 formation and arachidonic acid release in response to PAF and ANG II but not that to A 23187. PT pretreatment also inhibited formation of inositol trisphosphate (IP3) in response to ANG II or PAF but did not significantly alter the rise in intracellular calcium detected by fura-2. PT catalyzed ADP ribosylation of two proteins of molecular mass approximately 40 and 41 kDa. Further evidence for involvement of GTP-binding protein in phospholipase C activation was that GTP-gamma S stimulated IP3 generation. Immunoblots with antibodies directed against different inhibitory alpha subunits of GTP-binding proteins showed that the major 40-kDa PT substrate reacted with an antibody directed against a decapeptide of the G protein subunit alpha i2 that is also found in leukocytes. This was further confirmed by Northern blot that showed the existence of mRNA in mesangial cells that hybridized with a cDNA probe for G alpha i2. In addition lesser amounts of mRNA hybridized with a restriction fragment cDNA probe for G alpha i3, which corresponds to the 41-kDa substrate for PT ribosylation. These results show that phospholipase C activation by PAF and ANG II in mesangial cells involves a specific G protein, most likely G alpha i2.(ABSTRACT TRUNCATED AT 250 WORDS)
Bicarbonate reabsorption by the kidney of the newborn rabbit
Authors: van der Heijden A. J. , Guignard J. P.
Published: December 2017

Bicarbonate reabsorption by the immature kidney in response to acute acid-base changes was assessed in 50 anesthetized newborn rabbits before the end of nephrogenesis. The normal newborn rabbit (age 5-12 days) is in a state of hypochloremic metabolic alkalosis (PHCO3-, 31.9 +/- 0.6 mmol/l; PCl-, 83.1 +/- 1.0) and excretes a hypertonic (Uosmol = 578 +/- 41 mosmol/kgH2O), alkaline (UpH = 7.40 +/- 0.15) urine containing 50 +/- 9 mmol/l Cl- and 13 +/- 4 mmol/l Na+. The alkalosis is probably generated by an alkaline load contained in the mother's milk and maintained by a state of chloride wasting and volume contraction. In this alkalotic model, bicarbonate reabsorption, expressed per milliliter glomerular filtration rate (GFR), correlates positively with arterial CO2 pressure (PaCO2). The ability of the immature kidney to reclaim filtered bicarbonate in response to an elevation of the plasma carbon dioxide tension remains unlimited up to PaCO2 of 110 mmHg (y = 20.7 + 0.15 x, r = 0.82, P less than 0.001). Hypercapnia is associated with a marked fall in GFR, so that the positive correlation between bicarbonate reabsorption and PaCO2 vanishes when the bicarbonate reabsorption rate is expressed in absolute terms. Bicarbonate reabsorption is strongly dependent on the filtered load during both acutely induced metabolic acidosis and alkalosis. The acid-base state of the newborn rabbit is in sharp contrast with that of most animal species, and the renal handling of bicarbonate as a function of GFR does not show signs of tubular immaturity.
Dietary protein restriction and renal injury in the spontaneously hypertensive rat
Authors: Feld L. G. , Noble B. , Springate J. E. , Feldman M. J. , Van Liew J. B.
Published: December 2017

We examined the influence of a low-protein diet on the course of the renal injury in spontaneously hypertensive rats (SHR) and SHR given antihypertensive drug therapy (SHRD). Antihypertensive drug treatment was hydralazine, reserpine, and chlorothiazide. Wistar-Kyoto (WKY) rats served as normotensive controls. SHR, SHRD, and WKY were each placed on a 24, 14, and 10% protein diet at 5 wk and followed to 80-90 wk of age. Untreated SHR showed a steady rise in protein excretion from 5 to 70 wk regardless of dietary protein content. Protein excretion in SHRD on a 24% protein diet was similar to untreated SHR. However, SHRD on a 14 or 10% diet had a more moderate increase in protein excretion. Glomerular, tubular, and vascular pathology in untreated SHR was not influenced by dietary protein intake. Despite successful antihypertensive therapy, kidney pathology in SHRD on a 24% diet was not significantly different from untreated SHR. In contrast, SHRD on 14 or 10% protein diets had less segmental glomerulosclerosis and vascular pathology than untreated SHR. The results indicate that dietary protein restriction does not influence the course of renal injury in untreated SHR. However, the combination of antihypertensive drug therapy with protein restriction in SHR delays and may arrest progression of glomerulosclerosis and proteinuria.
Protection of the kidney against ischemic injury by inhibition of 5'-nucleotidase
Authors: Van Waarde A. , Stromski M. E. , Thulin G. , Gaudio K. M. , Kashgarian M. , Shulman R. G. , Siegel N. J.
Published: December 2017

We have evaluated the impact of inhibiting adenine nucleotide dephosphorylation on the metabolic and functional consequences of renal ischemia. Intramuscular injection of the ADP-analogue adenosine alpha, beta-methylene diphosphate (AMP-CP) achieved a 70% reduction in 5'-nucleotidase activity, as measured in crude extracts of rat kidney. AMPCP-treated animals had an increased residual nucleotide pool at the end of 45 min of ischemia compared with untreated rats. Assessment of renal ATP by 31P-nuclear magnetic resonance (31P-NMR) in vivo during reflow demonstrates the following: 1) higher rapid initial recovery of ATP (69.3 +/- 1.2 vs. 50.0 +/- 0.5% control value, P less than 0.005), 2) accelerated rate of ATP restoration (0.20 +/- 0.02 vs. 0.11 +/- 0.01% control/min, P less than 0.005), and 3) significantly enhanced renal ATP content after 120 min (93.6 +/- 2.0 vs. 63.1 +/- 0.7% control, P less than 0.005). Kidney function, as measured by the rate of inulin clearance 24 h after the insult, was also significantly improved in AMPCP-treated rats (725 +/- 50 vs. 313 +/- 28 microliters.min-1.100 g body wt-1). Thus inhibition of 5'-nucleotidase results in enhanced metabolic and functional recovery from a renal ischemic insult.
Volume and ion transport by fetal rat alveolar and tracheal epithelia in submersion culture
Authors: Krochmal E. M. , Ballard S. T. , Yankaskas J. R. , Boucher R. C. , Gatzy J. T.
Published: December 2017

The complex architecture of the mammalian lung has hindered measurements of permeability of and transport by the intact alveolar epithelium. We compared properties of fetal rat alveolar buds and tracheas in submersion culture by microelectrode and micropuncture techniques. Both alveolar buds and tracheas form cysts that accumulate liquid for up to 3 wk in culture. The transepithelial electric potential difference (PD) of alveolar buds and tracheas (lumen negative, 1.2-3.5 and 8-21 mV, respectively) was abolished by metabolic inhibitors or ouabain in the bath. Despite the difference in PDs, both epithelial regions, after 1 or 2 wk in culture, exhibited the following. 1) Cl- activities and concentrations in luminal liquid were 13 and 34% higher than the bathing medium; Na+ and K+ concentrations were not different. 2) Bumetanide inhibited PD by 70%, whereas terbutaline increased PD by 45%. 3) Amiloride injected into the cyst lumen induced a 20% decrease in the PD of 1-wk explants but did not affect 2-wk preparations. Replacement of bath Na+ by choline decreased the PD of tracheas by 85% but did not change alveolar PD in the presence or absence of bumetanide. The pattern of cyst liquid composition and PD responses to drugs suggests that fetal rat alveolar and tracheal epithelia secrete Cl-, which drives volume flow.
Interaction between loop of Henle flow and arterial pressure as determinants of glomerular pressure
Authors: Schnermann J. , Briggs J. P.
Published: December 2017

Experiments were performed in anesthetized rats to study the relationship between loop of Henle perfusion rate, arterial pressure, and stop-flow pressure (SFP) as an index of glomerular capillary pressure. In one set of experiments we measured the SFP feedback response to changes in loop perfusion at three levels of arterial pressure. The maximum SFP response fell significantly from 13.1 +/- 1.44 to 8.14 +/- 1.72 and 3.13 +/- 0.76 mmHg when arterial pressure was reduced from 118.1 +/- 1.27 to 98.8 +/- 0.51 and 78.8 +/- 1.72 mmHg. In other experiments arterial pressure was altered while loop perfusion rate was fixed at one of three levels. Without loop perfusion SFP changed with a slope of 0.27 +/- 0.04 mmHg/mmHg in the arterial pressure range between 80 and 130 mmHg. During perfusion at the flow rate at which response is half maximum, the slope was significantly reduced to 0.12 +/- 0.04. During perfusion at 45 nl/min, it was 0.03 +/- 0.05, a value not significantly different from zero. During dopamine administration (70 micrograms/kg min) SFP was pressure-dependent even during loop perfusion at 45 nl/min. These results show that arterial pressure determines TGF responsiveness and that the TGF signal determines the range of a regulatory input that is directly dependent on arterial pressure.
Operational modes of the organic anion exchanger in canine renal brush-border membrane vesicles
Authors: Steffens T. G. , Holohan P. D. , Ross C. R.
Published: December 2017

This study delineates the various operational modes catalyzed by the organic anion exchanger present in the canine renal brush-border membrane. The experiments examined the carrier-mediated effects of various organic and inorganic anions on the transport of either p-[3H]aminohippuric acid ([3H]PAH) or 36Cl-. [3H]PAH countertransport was significantly stimulated by PAH, urate, Cl-, Br-, HCO3-, and by a pH gradient. This pH stimulation remained in the absence of HCO3- (i.e., under N2), implying PAH-OH- exchange. Furosemide, bumetanide, penicillin, and probenecid inhibited countertransport of [3H]PAH. Likewise, the above anions produced cis inhibition of [3H]PAH transport. The cis and trans effects of SO4(-2) and formate were minimal. 36Cl- countertransport was stimulated by PAH, Cl-, Br-, HCO3-, formate, and by a pH gradient that was effective even in the absence of HCO3- (i.e., under N2), implying Cl- -OH- exchange. Cl- -OH- and Cl- -Cl- exchange was inhibited by PAH. In each instance, the trans-stimulation of 36Cl- efflux was insensitive to maneuvers that created an inside-positive membrane potential, demonstrating electroneutral mediated exchange. We conclude that the organic anion transporter can operate in three distinct exchange modes: organic-organic, organic-inorganic, and inorganic-inorganic.
The occurrence of nephrogenic diabetes insipidus in domestic fowl
Authors: Braun E. J. , Stallone J. N.
Published: December 2017

Nephrogenic diabetes insipidus (NDI) results from an inability of the kidney to concentrate the urine. The underlying cause of NDI is the failure of the collecting ducts to respond to antidiuretic hormone, however, the specific tubular defect is not well understood. In the present investigation an apparent case of NDI was studied in a strain of White Leghorn domestic fowl. In this strain, water intake of the males equaled 24.0% (controls 5.4%) of their body mass (BM) per day while that of the females equaled 51.4% (controls 11.7%) of their BM per day. Plasma osmolality (mosmol/kgH2O) of the NDI birds was significantly higher than that of controls (males 319 +/- 1.7 vs. 311 +/- 1.2; females 323 +/- 1.5 vs. 310 +/- 2.2). Urine osmolality of NDI birds was substantially lower than that of controls (males 90 +/- 6.2 vs. 524 +/- 4.0; females 70 +/- 4.7 vs. no value). In response to water deprivation, plasma osmolality of the NDI birds increased more markedly than that of the control animals (males 357 +/- 2.5 vs. 331 +/- 1.2; females 375 +/- 6.0 vs. 348 +/- 1.4 at 48 h of water deprivation). Basal plasma antidiuretic hormone (plasma arginine vasotocin, PAVT) levels in male NDI birds (9.9 +/- 0.7 microU/ml) and in female NDI birds (7.0 +/- 0.5 microU/ml) were nearly sixfold or nearly threefold higher, respectively, than in control birds. In response to water deprivation, PAVT of both NDI and control birds increased to similar levels, although the absolute increases in PAVT levels were substantially less in NDI birds.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of renal nerves in renal sodium retention of nephrotic syndrome
Authors: Herman P. J. , Sawin L. L. , DiBona G. F.
Published: December 2017

To define the role of the renal nerves in the renal sodium retention of the nephrotic syndrome, experiments were conducted in rats given adriamycin to produce nephrotic syndrome. All rats developed proteinuria and hypoalbuminemia and exhibited edema formation. Adriamycin-injected nephrotic rats were subjected to bilateral renal denervation (ADRIADNX) or sham renal denervation (ADRIASHAM). Rats injected with adriamycin vehicle were subjected to bilateral renal denervation (DNX) or sham renal denervation (SHAM). Metabolic balance studies were carried out in all rats beginning on the 8th day after bilateral or sham renal denervation. Dietary sodium content was 210 meq/kg Na on days 8-12 and days 24-26 and was 10 meq/kg Na on days 13-23. Nephrotic rats demonstrated significantly greater overall (19 days) cumulative sodium balance than vehicle control rats, ADRIASHAM 8.47 +/- 0.81 vs. SHAM 5.74 +/- 0.34 meq Na, P less than 0.01. Bilateral renal denervation did not significantly affect overall cumulative sodium balance in the vehicle control rats, DNX 6.15 +/- 0.71 vs. SHAM 5.74 +/- 0.34 meq Na. However, bilateral renal denervation significantly decreased overall cumulative sodium balance in the nephrotic rats, ADRIADNX 6.59 +/- 0.56 vs. ADRIASHAM 8.47 +/- 0.81 meq Na, P less than 0.01. Results indicated that the increased renal sodium retention characteristic of nephrotic syndrome is dependent, in large part, on increased efferent renal sympathetic nerve activity.
Net calcium efflux from live bone during chronic metabolic, but not respiratory, acidosis
Authors: Bushinsky D. A.
Published: December 2017

In vivo chronic metabolic acidosis induces bone mineral dissolution. Whether the dissolution is due to alterations in physicochemical factors alone, as in acute metabolic acidosis, or requires participation of bone cells is not clear. The effect of chronic respiratory acidosis on bone has also not been established. To determine the effects of chronic metabolic and respiratory acidosis on net calcium flux from bone, we cultured live and dead neonatal mouse calvariae for 99 h in control medium or in medium acidified (pH approximately equal to 7.1) either by lowering the bicarbonate concentration (Met) or by increasing the PCO2 (Resp). We measured net calcium flux (JCa) over 0-48, 48-96, and 96-99 h. Over the first 48 h, there was greater net calcium efflux from live and dead Met than from both Resp groups. All four acidic groups had greater net calcium efflux than controls. Over the last 51 h of the chronic 99 h culture, there was net calcium efflux only from live Met (JCa = 285 +/- 129 nmol.bone-1.3 h-1) and not from any of the other groups (live control, JCa = -183 +/- 24; live Resp, JCa = -110 +/- 22; dead control, JCa = -256 +/- 12; dead Met, JCa = 11 +/- 78; dead Resp, JCa = -27 +/- 47; each P less than 0.02 vs. live Met). There is net calcium efflux from live cultured neonatal mouse calvariae during chronic metabolic, but not respiratory, acidosis. During chronic acidosis, decreased medium bicarbonate, and not just a fall in pH, is necessary to enhance net calcium efflux from live bone.
Sorbinil prevents glomerular hyperperfusion in diabetic rats
Authors: Bank N. , Mower P. , Aynedjian H. S. , Wilkes B. M. , Silverman S.
Published: December 2017

The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.
Oscillations of tubular pressure, flow, and distal chloride concentration in rats
Authors: Holstein-Rathlou N. H. , Marsh D. J.
Published: December 2017

Previous experiments have shown oscillations in proximal tubular pressure in halothane-anesthetized rats. Such oscillations should be due to oscillations in flow rate and should cause periodic oscillations in both distal tubular chloride concentration and distal tubular pressure. The purpose of the study was to test these predictions. In halothane-anesthetized Sprague-Dawley rats, distal tubular chloride activity was measured with Cl- -sensitive electrodes, and late proximal flow rate was measured by pulse injection of boluses of solutions containing rhodamine dextran. Bolus velocity was detected by videomicroscopy. The time resolution was 2 s. All four variables oscillated with the same frequency, approximately 35 mHz. The amplitude of the flow and the chloride oscillations were 28 and 10%, respectively, of the mean values. Proximal fluid velocity led proximal pressure by 1.5 +/- 0.4 s, whereas distal chloride activity lagged proximal pressure by 8.9 +/- 0.8 s. The distal pressure lagged the proximal pressure by 1.05 +/- 0.38 s. It is concluded that there is a significant variation in distal chloride activity, the magnitude of which appears to be sufficient to account for the observed flow variations through the operation of the tubuloglomerular feedback mechanism.
Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II
Authors: Carmines P. K. , Navar L. G.
Published: December 2017

Previous reports have suggested that organic calcium antagonists only partially inhibit the renal hemodynamic actions of angiotensin II (ANG II). This study tested the hypothesis that the calcium antagonist-sensitive component of ANG II-induced vasoconstriction is localized at a preglomerular site. Videomicroscopic measurements of vascular dimension were performed on in vitro blood-perfused juxtamedullary nephrons from captopril-treated rats. Under control conditions, afferent and efferent arteriolar diameters averaged 23.0 +/- 1.6 and 21.2 +/- 2.2 microns, respectively. Topical application of 0.1 nM ANG II decreased the diameters of afferent (-17 +/- 2%) and efferent (-15 +/- 3%) arterioles. Both 50 microM verapamil and 10 microM diltiazem dilated afferent arterioles. Verapamil also elicited a modest efferent vasodilation. In the presence of either verapamil or diltiazem, the effect of ANG II to decrease efferent diameter was sustained (-15 +/- 4%); however, the effect of ANG II on afferent diameter was abolished (-1 +/- 1%). These observations document differential influences of calcium channel blockers on ANG II-mediated vasoconstriction and suggest that the pre- and postglomerular vasoconstrictor actions of ANG II may occur through different calcium entry or mobilization mechanisms.
Endothelin: a potent renal and systemic vasoconstrictor peptide
Authors: King A. J. , Brenner B. M. , Anderson S.
Published: December 2017

Endothelin is an endothelial cell-derived peptide recently shown to possess potent vasoconstrictor properties. Bolus intravenous injections of endothelin (5-450 pmol) into anesthetized Munich-Wistar rats induced a marked pressor effect, the magnitude and duration of which were dose dependent. Maximal systemic and renal responses occurred within 20 min and persisted for greater than 90 min in the higher dose range. In response to bolus dosages of 25 pmol or greater, renal plasma flow fell proportionately more than glomerular filtration rate, resulting in an increase in filtration fraction. In micropuncture studies of rats given continuous intravenous infusions of endothelin (0.63 pmol/min), the peptide caused a proportionately greater elevation of efferent than afferent arteriolar resistance, with a marked elevation of glomerular capillary hydraulic pressure and a lower glomerular capillary ultrafiltration coefficient. Endothelin was modestly natriuretic when systemic pressure rose and renal function was not severely impaired. This potent renal and systemic vasoconstrictor may play an important role in glomerular injury and in the pathophysiology of a variety of clinical microvasculopathies.
Colloid osmotic pressure in young analbuminemic rats
Authors: Joles J. A. , Willekes-Koolschijn N. , Braam B. , Kortlandt W. , Koomans H. A. , Dorhout Mees E. J.
Published: December 2017

Colloid osmotic pressure (COP) was measured in plasma and interstitial fluid (subcutaneous wick) from 8 to 75 days of age in Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR). In all animals plasma COP (approximately 10 mmHg at 8 days of age) increased during growth. In the female NAR the rise in nonalbumin proteins was so large that at 75 days the plasma COP was not lower than in the SDR; whereas in male NAR a difference of approximately 4 mmHg remained. Interstitial COP increased with aging in the SDR, but not in the NAR. This resulted in equal transcapillary COP gradients in 75-day-old male and female SDR and male NAR (approximately 11–12 mmHg) but a somewhat larger gradient in the female NAR (approximately 14 mmHg). Blood pressure and plasma volume were not low in the NAR. Extracellular fluid volume (as a percentage of body weight) was similar in all groups and decreased with age. Clearances of 51Cr-labeled EDTA and 125I-labeled hippuric acid were decreased in young (45 day) NAR vs. young SDR, but not at 75 days of age. In conclusion, NAR are able to maintain a normal transcapillary COP gradient, and do not display signs of abnormal volume regulation during early development.
Ca2+ absorption in the pars recta of cortical S2 rabbit proximal tubules: role of diffusion
Authors: Sacks P. , Bourdeau J. E.
Published: December 2017

Individual partes rectae of cortical S2 proximal tubules were dissected from rabbit kidneys and perfused in vitro. The bath was a protein-free, plasmalike solution, whereas the perfusate simulated "late" proximal tubular fluid (high [Cl-], low [HCO3-], absence of Na+-cotransported solutes). Transepithelial voltages at the perfusion and collection ends were measured simultaneously in doubly cannulated tubules. Ionized calcium concentrations in perfusates, collectates, and the bath were calculated from measurements of calcium ion activities made in situ with Ca2+-selective microelectrodes. Epithelial calcium permeability was estimated from the bath-to-lumen movement of 45Ca. Total calcium concentrations of perfused and collected fluids were measured by continuous-flow microcolorimetry. Under these conditions there was a lumen-positive transepithelial voltage that was equal at both ends of the tubules. Luminal [Ca2+] [corrected], which decreased along the length of the tubule, was greater than that of the bath. Using the measured calcium permeability, we calculated the diffusional component of the net calcium absorptive flux from the mean transepithelial delta [Ca2+] and the measured transepithelial voltage. We found that ionic diffusion accounted for the net flux, suggesting that diffusion is the primary mechanism of calcium absorption in this segment of the rabbit nephron.
Role of ANP in natriuresis of head-out immersion in humans
Authors: Rabelink T. J. , Koomans H. A. , Boer P. , Gaillard C. A. , Dorhout Mees E. J.
Published: December 2017

Atrial natriuretic peptide (ANP) may play a role in the natriuresis after acute circulatory challenges. To assess this role in head-out water immersion (HOI), we compared in clearance studies the effect of 3 h HOI with an equally natriuretic 3-h infusion of ANP [0.01 microgram.kg-1.min-1 human ANP-(99-126)] in seven healthy individuals taking a 100 mmol sodium diet. The studies were repeated after treatment with enalapril (20 mg twice daily), which in previous studies inhibited the natriuresis after ANP. HOI caused a natriuresis equal to that of ANP infusion despite an about five times smaller rise in plasma ANP. HOI increased and ANP decreased estimated renal plasma flow (ERPF). HOI increased maximal free water clearance and decreased fractional lithium reabsorption. ANP did not affect these variables but raised minimal urine osmolality. Enalapril enhanced the fall in ERPF caused by ANP and abolished its natriuretic effect; enalapril did not impair either the natriuresis after HOI or the increase in ERPF and the fall in lithium reabsorption. These data indicate that the low dosage of ANP causes natriuresis by reducing sodium absorption in a distal nephron target segment; enalapril impairs this effect, perhaps by enhancing ANP-induced vasoconstriction, which decreases delivery to this target segment. HOI, by increasing sodium delivery to this segment, is natriuretic despite only a small rise in plasma ANP. Enalapril does not impair these effects. Although a rise in plasma ANP may be one factor in the natriuresis of HOI, the present data speak against an exclusive role. Other factors determine the magnitude of the natriuretic response.
Studies of the mitogenic effect of serotonin in rat renal mesangial cells
Authors: Takuwa N. , Ganz M. , Takuwa Y. , Sterzel R. B. , Rasmussen H.
Published: December 2017

A vasoactive inflammatory amine, serotonin, stimulates DNA synthesis in rat glomerular mesangial cells in a dose-dependent manner and acts synergistically with either insulin or epidermal growth factor (EGF). The combined effects of 10(-6) M serotonin and these peptide hormones are nearly equal to those induced by 10% fetal bovine serum. Serotonin stimulates the turnover of polyphosphoinositols resulting in a transient rise in intracellular free Ca2+ concentration, as measured either with the photoprotein aequorin, or with fura-2. This is accompanied by a transient increase in 45Ca2+ efflux from prelabeled cells. Serotonin also induces a prompt and sustained threefold increase in Ca2+ influx rate across the plasma membrane and a rapid and sustained twofold increase in cellular 1,2-diacylglycerol content. In addition, there is an increase in the extent of phosphorylation of an acidic 80-kDa protein, a putative substrate for protein kinase C. Activators of protein kinase C (including phorbol 12-myristate 13-acetate or 1,2-dioctanoylglycerol) mimic the mitogenic effect of serotonin. The effect of serotonin on cell proliferation is partially inhibited in a reversible manner by LiCl. Treatment of mesangial cells with insulin plus EGF for 60 min leads to a small but consistent increase in the content of inositol phosphates and 1,2-diacylglycerol. Their effects are additive to those of serotonin. Moreover, insulin and EGF significantly stimulate the phosphorylation of the 80-kDa protein, and potentiate the serotonin-induced phosphorylation of this protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct measurement of basolateral membrane potentials from cells of the macula densa
Authors: Bell P. D. , Lapointe J. Y. , Cardinal J.
Published: December 2017

At the present time, little is known concerning the electrophysiology of the cells of the macula densa and whether or not these cells are electrically responsive to alterations in luminal fluid composition. To investigate this issue, cortical thick ascending limbs (CTAL) containing macula densa and attached glomeruli were dissected from rabbit kidney and the CTAL perfused in vitro. Basolateral membrane potential (Vbl) was measured with microelectrodes in macula densa cells and, for comparison, in cells of the CTAL. Macula densa Vbl averaged -56.5 +/- 7.6 mV (n = 4) at a (n = 22) at 20 mM NaCl, -35.6 +/- 3.9 mV (n = 16) at 45 mM NaCl, and -25.5 +/- 2.6 mV (n = 32) at 150 mm NaCl. Thus macula densa Vbl depolarized markedly (31 mV) when luminal perfusate [NaCl] was increased from low to high values. In contrast, Vbl measured in CTAL cells averaged -62 +/- 6.1 mV (n = 6) in 45 mM NaCl and did not change significantly as perfusate NaCl was increased to 150 mM. In the presence of 150 mM NaCl, luminal application of furosemide (50 microM) produced a small (3.5 +/- 1.1 mV, n = 16) but statistically significant (P less than 0.02) hyperpolarization in macula densa cells, whereas CTAL cell Vbl hyperpolarized markedly (20 +/- 5.7 mV, n = 6) with addition of furosemide. Finally, neither macula densa cells nor the CTAL cells changed Vbl when 45 mM NaCl solution was made hypotonic by removing mannitol.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of acetate on luminal acidification processes in the S3 segment of the rabbit proximal tubule
Authors: Geibel J. , Giebisch G. , Boron W. F.
Published: December 2017

We determined that, in the nominal absence of HCO-3, acetate (Ac-) doubles luminal acidification in the S3 segment of the rabbit proximal tubule. This stimulation had two components, one that was dependent on Na+ and luminal Ac- and a second that was independent of Na+ but dependent on basolateral Ac-. In the presence of 25 mM HCO-3, Ac- did not stimulate acid secretion (i.e., HCO-3 reabsorption), but actually inhibited it. The inhibition was 35% with bilateral Ac- and 15% with basolateral Ac-. The effects of Ac- were reversible both in the absence and presence of HCO-3, and are present at concentrations as low as 1 mM. We conclude that acetate (i.e., monocarboxylates) has a significant effect on luminal acidification processes both in the presence and absence of HCO-3.
Renal responses to mental stress and epinephrine in humans
Authors: Tidgren B. , Hjemdahl P.
Published: December 2017

Renal blood flow, renal sympathetic nerve activity, and renin release responses to mental stress (Stroop's color-word conflict test; CWT) and intravenously infused epinephrine (Epi) were evaluated in 12 healthy volunteers. The overflows of norepinephrine (NE) and dopamine (DA) to renal venous plasma were measured as indexes of nerve activity; the fractional extraction of Epi was used to assess renal catecholamine extraction from arterial plasma. At rest, NE and DA levels were higher in renal venous plasma than in arterial plasma. Arterial Epi levels were 0.26 +/- 0.04 nmol/l, and the fractional extraction of Epi by the kidney was 46 +/- 4%. CWT increased renal vascular resistance (RVR) by 48%, renal venous NE overflow by 214% (to 708 +/- 79 pmol/min), and DA overflow by 42% (to 34 +/- 4 pmol/min). Arterial Epi increased by 197%. The vasoconstrictor response was correlated with the NE overflow response. The increased renin release (from 75 to 247 U/min, median values; P less than 0.001) was correlated to increases in mean arterial pressure and NE and DA overflows. Epi infusion increased arterial plasma Epi and renin release dose dependently to 6.43 +/- 0.27 nmol/l and by 664%, respectively. RVR and NE and DA overflows were unchanged. Renal venous DA data support the existence of a subset of renal dopaminergic nerves. Mental stress causes renal vasoconstriction, apparently due to increased renal sympathetic nerve activity. Physiological increments of circulating Epi do not affect renal blood flow but enhance renin release markedly without apparent activation of the renal nerves in humans.
Osmoregulation of thirst and vasopressin release in pregnancy
Authors: Lindheimer Marshall D. , Barron William M. , Davison John M.
Published: December 2017

Pages F159-F169: Marshall D. Lindheimer, William M. Barron, and John M. Davison. “Osmoregulation of thirst and vasopressin release in pregnancy.” Page F161: Figure 3, legend should read [Reprinted with permission from J. Clin. Invest., vol. 68, p. 337-346, 1981 (32).]. Page F161: last paragraph, 5th line should read “(Uosmol 147 ± 40 and 167 ± 43 mosmol/kg ... ).”