bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional correlates of effects of angiotensin-induced changes in rat glomerulus
Authors: Haley D. P. , Sarrafian M. , Bulger R. E. , Dobyan D. C. , Eknoyan G.
Published: December 2017

The effects of systemically infused angiotensin II (ANG II) (5, 50, and 100 ng X min-1 X 100 g body wt-1; groups 1, 2, and 3, respectively) were studied in Sprague-Dawley rats. All doses increased systemic blood pressure, fractional excretion of sodium, and urine flow rate but decreased glomerular filtration rate. Scanning electron microscopy revealed no detectable changes in the visceral epithelium or measurable alterations in the total area of endothelial capillary surface occupied by pores. Glomerular basement membrane surface densities of outer (OCG) and inner (ICG) cortical glomeruli averaged 0.22 micron2/micron3 of glomerular tuft volume in all groups. Volume ratios of the individual glomerular tufts to that of their Bowman's capsule of OCG were less (P less than 0.05) in groups 1 and 2 (52 +/- 3 and 63 +/- 9%) than the control group (72 +/- 1%). The volume fraction of the glomerular capillaries to their Bowman's capsules remained approximately 25% in all groups. However, the volume fraction of parenchyma to Bowman's capsule was reduced in group 1 to 30 +/- 4% and 38 +/- 5% in group 2 compared with the control value of 47 +/- 2% (P less than 0.05). Thus ANG II reduced glomerular tuft volume and parenchyma but did not alter filtration surface area or capillary endothelial epithelial surface characteristics.
Water permeability and particle aggregates in ADH-, cAMP-, and forskolin-treated toad bladder
Authors: Kachadorian W. A. , Coleman R. A. , Wade J. B.
Published: December 2017

Osmotic water flow was used to evaluate total tissue water permeability (Ptissue), and luminal membrane particle aggregates, presumed sites for transmembrane water movement, were quantified to assess luminal membrane water permeability, in bladders treated with maximally stimulating concentrations of antidiuretic hormone (ADH), adenosine 3',5'-cyclic monophosphate (cAMP), and forskolin. Aggregates were as numerous and occupied the same fractional area of the luminal membrane in response to cAMP treatment (10 mM) as treatment with ADH (20 mU/ml). Ptissue in cAMP-treated tissues, however, was only half of that induced by ADH (P less than 0.001). A similar disparity in the relationship between aggregates and Ptissue occurred for additional bladders treated with 50 microM forskolin, which is known to increase endogenous cAMP to levels much greater than caused by maximally stimulating concentrations of ADH. Although Ptissue achieved with forskolin was the same in paired bladders treated with ADH, aggregates were far more numerous (P less than 0.05) and occupied much more membrane area (P less than 0.05) with forskolin. These observations are consistent with the view that aggregate appearance in the luminal membrane is a function of intracellular cAMP. The finding that the hydrosmotic response of toad bladder to both cAMP and forskolin compared with ADH stimulation is reduced relative to measured changes in luminal membrane aggregates suggests that the effect of ADH in altering water permeability involves additional regulation via a non-cAMP-mediated mechanism. This latter event would appear to be by an effect of ADH on the permeability of a resistance at a postluminal membrane site and/or possibly on the permeability of aggregates in the luminal membrane.
Effect of acute hypercapnia on PTH-stimulated phosphaturia in dietary Pi-deprived rat
Authors: Guntupalli J. , Matthews B. , Carlin B. , Bourke E.
Published: December 2017

The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.
Facilitated transfer of glucose from blood into perilymph in the rat cochlea
Authors: Ferrary E. , Sterkers O. , Saumon G. , Tran Ba Huy P. , Amiel C.
Published: December 2017

The transport of glucose into cochlear endolymph, perilymph of scala vestibuli and perilymph of scala tympani, and cerebrospinal fluid (CSF) was studied after intravenous administration of tracers of D-glucose, L-glucose, and 3-O-methyl-D-glucose in anesthetized rats. The data showed that D-glucose concentrations in perilymph of scala vestibuli, perilymph of scala tympani, and CSF were approximately 50%, and in endolymph less than 10%, that in plasma; D-glucose concentration in perilymph of scala vestibuli, perilymph of scala tympani, and CSF increased as a linear function of that in plasma; D-glucose entry into perilymph of scala vestibuli, perilymph of scala tympani, and CSF was more rapid than that of L-glucose; after infusion of 3-O-methyl-D-glucose, but not after that of mannitol, both the D-glucose concentration ratio of perilymph over plasma and D-glucose transfer into perilymph were lowered. These results indicate that D-glucose enters into perilymph of scala vestibuli by a facilitated transport, possibly located at the blood-perilymph barrier.
Immunochemical characterization of a band 3-like anion exchanger in collecting duct of human kidney
Authors: Wagner S. , Vogel R. , Lietzke R. , Koob R. , Drenckhahn D.
Published: December 2017

Poly- and monoclonal antibodies have been prepared against the cytoplasmic domain (43 kDa) and the 17-, 20-, and 35-kDa fragments of the membrane-spanning domain of the human erythrocyte anion exchanger, band 3. The antibodies were used to localize and further characterize analogues of band 3 in the human kidney. We report here that the basolateral membrane of intercalated cells of the connecting tubules and collecting ducts contains an analogue of band 3 that appears to be highly homologous to the erythrocyte anion exchanger. This band 3-like protein is probably important for reabsorption of bicarbonate in the collecting duct system and thus for acidification of the forming urine. The band 3-like protein of the intercalated cells contain immunoreactive sites of both the cytoplasmic domain and the three major fragments of the membrane-spanning domain of erythrocyte band 3. Although no immunological differences were detected between the membrane-spanning domains of band 3 in erythrocytes and intercalated cells, there are at least three sites along the cytoplasmic domain of kidney band 3 that differ from erythrocyte band 3 in either amino acid composition or posttranslational modifications. The main kidney analogue of band 3 that contains epitopes of the cytoplasmic domain as well as the 17- and 35-kDa membrane-spanning domain of erythroid band 3 is a polypeptide with an apparent molecular mass of 100-110 kDa. Further immunoreactive polypeptides at approximately 180, approximately 140, approximately 38, approximately 25-30 kDa that were detected at lower stringency and higher sensitivity of the immunoblotting procedure may be members of a multigene family that encodes a series of related proteins.
Uninephrectomy and dietary protein affect fluid absorption in rabbit proximal straight tubules
Authors: Johnston J. R. , Brenner B. M. , Hebert S. C.
Published: December 2017

To further delineate the mechanisms involved in the renal compensatory response to renal mass ablation, we evaluated the interactions of protein intake and uninephrectomy on total, active, and passive fluid absorption (Jv) in the in vitro perfused superficial proximal straight tubule (SFPST) isolated from sham-operated or uninephrectomized rabbits pair fed 7, 14, or 45% protein diets. In all protein groups, we observed significant increases in Jv and in cell height from SFPST segments obtained from remnant renal tissue harvested 3 wk post-uninephrectomy when compared with sham-operated controls. Uninephrectomy also led to compensatory hypertrophy of whole-kidney mass and to elevations in inulin clearances. Increased protein intake consistently enhanced these renal and SFPST structural and functional changes, whereas protein restriction limited compensatory responses. The changes in Jv following uninephrectomy were attributable to increases in the active, but not the passive, component of Jv in all protein groups. Moreover, the active component of Jv could be modified by altering dietary protein intake. Single kidney inulin clearances were correlated with the changes in total Jv with ultrafiltrate perfusate (r = 0.88; P less than 0.025), with artificial perfusate (r = 0.95; P less than 0.01), the active component of Jv (r = 0.96; P less than 0.005), SFPST cell height (r = 0.94; P less than 0.01), and whole-kidney weight (r = 0.99; P less than 0.005). These results indicate that hypertrophy of renal structure and augmentation of function following uninephrectomy and increased dietary protein are also observed in single rabbit SFPST segments perfused in vitro; that the hypertrophic responses following uninephrectomy can be enhanced or reduced by increases or decreases in protein intake, respectively; and that these changes are paralleled by changes in glomerular filtration rate.
Bicarbonate and ammonia transport in isolated perfused rat proximal straight tubules
Authors: Garvin J. L. , Knepper M. A.
Published: December 2017

Bicarbonate, ammonia, and fluid transport were studied in isolated perfused proximal straight tubules from rats. The mean rate of fluid absorption (0.77 nl X min-1 X mm-1) and the mean rate of total CO2 absorption (42 pmol X min-1 X mm-1) exceeded corresponding rates measured previously in rabbit proximal straight tubules. The limiting total CO2 concentration when the tubules were perfused at slow flow rates was 5 mM, a value similar to those reported previously for rat proximal convoluted tubules and thick ascending limbs. When rat proximal straight tubules were perfused and bathed with solutions containing 1 mM total ammonia at slow perfusion rates, the measured total ammonia concentration in collected fluid rose to a level predicted by the diffusion trapping model of ammonia secretion in the absence of a luminal disequilibrium pH. We conclude the proximal straight tubule of the rat can absorb bicarbonate at a rate that can account for a large portion of the bicarbonate absorption measured in vivo between the late proximal convoluted tubule and the early distal tubule, the rat proximal straight tubule is capable of transepithelial ammonia secretion, most likely by NH3 diffusion down a concentration gradient generated by luminal acidification, and the rat proximal straight tubule apparently does not generate a luminal disequilibrium pH despite the occurrence of proton secretion, implying the presence of endogenous luminal carbonic anhydrase.
Measurement of flow rate in rat proximal tubules with a nonobstructing optical method
Authors: Chou C. L. , Marsh D. J.
Published: December 2017

A method was developed for measuring volume flow rate in free-flowing proximal tubules. Multiple injections of a solution containing fluorescein isothiocyanate-dextran (mol wt 20,000) were made into the tubular fluid stream while fluorescence was detected by videomicroscopy. Progression of the dye bolus between two points along the tubule was measured to determine fluid velocity. Tubule diameter was measured by video image shearing and flow rate was calculated from the product of velocity and cross-sectional area. The technique was validated by simultaneous collections in the same tubule just downstream. There was good correlation between the results obtained with the two methods (r = 0.89). The estimated average injection volume was 0.0165 +/- 0.00016 nl. An increase in tubular volume flow caused by repetitive injections during micropuncture collections was too small to be detected. This new method should be useful in experimental situations that require uninterrupted delivery of fluid to the macula densa, or when better temporal resolution is required than can be obtained with the conventional method.
Segmental synthesis and actions of prostaglandins along the nephron
Authors: Bonvalet J. P. , Pradelles P. , Farman N.
Published: December 2017

The sites of synthesis and action of prostaglandins (PGs) along the renal tubule are examined. We focused our attention on experiments performed on well-defined nephron segments, using direct quantitative measurements of prostaglandin synthesis by radio- or enzyme-immunoassay. On the other hand, we selected, among the described effects of PGs, those obtained on precisely defined tubular segments. Among PGs, PGE2 synthesis is largely predominant all along the tubule. Its main sites of synthesis are the medullary collecting tubule and, to a lesser extent, the cortical collecting tubule and the thin limb of Henle's loop. Synthesis of PGE2 is amplified approximately tenfold in the presence of an excess exogenous substrate, arachidonic acid, compared with values measured without addition of substrate. Other eicosanoids have roughly the same distribution along the tubule as PGE2. Their rate of synthesis is, however, much less than that of PGE2, approximately 20-fold lower for PGF2 alpha and 6-keto-PGF1 alpha, and 100-fold lower for thromboxane B2 (TxB2). This contrasts with glomerular PG synthesis, where the difference between the production of PGE2 and other eicosanoids is much less marked. Most studies agree that antidiuretic hormone (ADH) and kinins augment PGE2 synthesis, whereas corticosteroids decrease it, at least in the collecting tubule. Direct effects of PGE2 have been described mainly in the medullary thick ascending limb and collecting tubule. They generally consist of a decrease in transepithelial potential difference and reabsorptive rates of water and solutes, in particular sodium and chloride. However, whatever the solute or tubular segment concerned, some studies failed to find such effects. The bulk of evidence suggests that ADH and PGs interact in kidney tubular cells. It is generally accepted that PGs antagonize the hydrosmotic effects of ADH in the collecting tubule. The mechanisms underlying these complex interactions are still under discussion: they probably involve several types of receptors and pathways for ADH action, which intervene in the modulation of both PG synthesis and cyclic nucleotides, and several types of PG receptors, either stimulatory or inhibitory to adenylate cyclase.
Effects of cadmium on canine renal cortical adenylate cyclase
Authors: Lundberg U. , Milanes C. L. , Pernalete N. , Weisinger J. R. , Contreras N. E. , Paz-Martinez V. , Bellorin-Font E.
Published: December 2017

The present studies examine the effects of cadmium (Cd2+) on adenylate cyclase activity in basolateral renal cortical membranes from normal dogs. Cd2+, in the dose range of 1 to 200 microM caused a dose-dependent inhibition of adenylate cyclase activity due to competitive inhibition with respect to the allosteric activator Mg2+ (increase in the Kact for Mg2+ from 13.8 to 37.2 mM). In addition, increasing Cd2+ concentrations from 0 to 25 microM resulted in a purely competitive inhibition with respect to ATP. The Km for ATP increased from 61 to 128 microM. When Mn2+ at a concentration of 20 mM was substituted for Mg2+, Cd2+ maintained its inhibitory effect at concentrations lower than 25 microM. At higher concentrations it stimulated enzyme activity in a dose-dependent fashion. In the absence of other divalent cations Cd2+ was a potent stimulator of basal adenylate cyclase activity, far more potent than the physiological activator of the system Mg2+. Kact for Cd2+ was 1.0 mM (Kact for Mg2+ 20 mM), whereas the Vmax showed a fourfold increase compared with the Mg2+-stimulated membranes. However, under these conditions, synthetic bovine parathyroid hormone (1-34) or 5'-guanylylimidodiphosphate did not stimulate adenylate cyclase. It is concluded that Cd2+ behaves as a partial agonist in this system, due to its ability to form a new enzymatic substrate complex: Cd-ATP, which competes with the physiological substrate Mg-ATP at the catalytic site of the enzyme. In addition, Cd2+ in the absence of other divalent cation stimulates basal enzyme activity, presumably through interaction at an additional site, closely related to the allosteric metal regulatory site of this enzyme system.
Renal autoregulation and pressure natriuresis during ANF-induced diuresis
Authors: Paul R. V. , Kirk K. A. , Navar L. G.
Published: December 2017

We examined the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) in the anesthetized dog during selective renal arterial infusion of two different synthetic atrial natriuretic factor (ANF) analogues. Rat atriopeptin II (5 X 10(-8) M in renal arterial blood) caused increases in sodium and water excretion but left RBF and GFR unchanged. A similar response was seen with rat 8-33 atrial natriuretic peptide (ANP) (10(-9) M), but a twofold higher dose of this peptide produced a transient increase in RBF and a sustained 16% increase in GFR. The normal pattern of RBF autoregulation in response to decreases in renal perfusion pressure was not altered by either peptide. GFR was also efficiently autoregulated during ANF infusion; however, there was a threefold increase in the slope of the relationship between sodium excretion and arterial pressure (pressure natriuresis) during 8-33 ANP infusion (control 1.11 +/- 0.39, 8-33 ANP 4.00 +/- 0.86 mu eq/mmHg, P less than 0.01). We conclude that ANF-induced diuresis can be sustained without detectable changes in either the autoregulation-responsive or autoregulation-independent components of renal vascular resistance. Factors other than GFR, which are highly responsive to renal perfusion pressure, are important in modulating the natriuresis caused by ANF. The augmentation of pressure natriuresis within the GFR autoregulatory range suggests an influence of ANF on the magnitude of arterial pressure-induced changes in tubular sodium reabsorption.
Potassium channels in Necturus proximal tubule
Authors: Kawahara K. , Hunter M. , Giebisch G.
Published: December 2017

Potassium channels from the apical and basolateral membranes of Necturus proximal tubule were studied using the patch-clamp technique. The conductance of the basolateral channel was dependent on the pipette K+ concentration (apparent Km, 65.5 mM K+; maximum channel conductance, 49.8 pS). The permeability ratio (PK+/PNa+) was approximately 10:1. The fractional open time increased with hyperpolarization, whereas mean open times did not change. Ba2+ (0.1 mM pipette concentration) blocked the channel and reduced the mean open time. The apical K+ channel was activated with depolarization and had a slope conductance of 60 pS in the inside-out configuration (100 mM KCl in the pipette and 2.5 mM KCl in the bath). The K+-Na+ selectivity ratio was 32:1. These different channel types will allow independent control of the apical and basolateral membrane K+ conductances.
Effect of adrenalectomy on NEM-sensitive ATPase along rat nephron and on urinary acidification
Authors: Khadouri C. , Marsy S. , Barlet-Bas C. , Doucet A.
Published: December 2017

An N-ethyl-maleimide (NEM)-sensitive ATPase that displays the properties of an electrogenic proton pump has been described in the different segments of the rat nephron where it mediates part of the active tubular proton secretion. Because corticosteroids are known to control kidney acidification, we evaluated whether or not NEM-sensitive ATPase is a target of corticosteroids in some nephron segments. For this purpose we measured NEM-sensitive ATPase activity in the different segments of nephron microdissected from normal and adrenalectomized rats. Results indicate that within 1 wk after adrenalectomy NEM-sensitive ATPase activity was markedly decreased in both cortical and outer medullary portions of the collecting tubule (cortex, from 398 +/- 12 (+/-SE) to 145 +/- 20; outer medulla, from 293 +/- 21 to 112 +/- 14 pmol X mm-1 X h-1); however, it was not altered in any other segment of the nephron. These results demonstrate that kidney NEM-sensitive ATPase is under the control of corticosteroids and suggest that mineralocorticoids rather than glucocorticoids are involved in this regulation that specifically occurs in mineralocorticoid-sensitive nephron segments. This paper also describes a new computerized method for the automatic determination of the length of single nephron segments.
Chloride-dependent potassium secretion in early and late renal distal tubules
Authors: Velazquez H. , Ellison D. H. , Wright F. S.
Published: December 2017

Potassium transport by subsegments of the rat surface distal tubule was studied using a modified in vivo microperfusion method. The nephron segments between 14 and 38% and between 62 and 83% of total distal length distance between macula densa region and confluence of tubule with another) were perfused separately. The first of these two segments is composed primarily of distal convoluted tubule (DCT) cells; the more distal segment is made up primarily by initial collecting tubule (ICT) epithelium. Experiments were performed to measure potassium secretion via two pathways: a diffusion mechanism driven by a favorable electrochemical gradient for potassium, and a cotransport mechanism activated when lumen chloride concentration is low. In a first series of experiments, both the DCT and the ICT secreted potassium when perfused with an artificial control solution resembling fluid normally present at the beginning of the distal tubule. Absolute rates of potassium secretion were higher in the ICT than in the DCT. Decreasing lumen Cl concentration stimulated potassium secretion more in the ICT than in the DCT. In a second series of experiments, the subsegments were perfused with a solution in which ion concentrations were raised to levels found in interstitial fluid. Under these circumstances, potassium secretion was lower in both segments. Decreasing lumen Cl concentration resulted in higher rates of potassium secretion in the DCT than those seen in the first series with low chloride; rates of potassium secretion in the ICT were as high as in the first series.(ABSTRACT TRUNCATED AT 250 WORDS)
A model of osmotic and hydrostatic pressure effects on volume absorption in the proximal tubule
Authors: Williams J. C. , Schafer J. A.
Published: December 2017

A computer model of the proximal tubule of the rabbit is described in which the tubule is treated as a single cylindrical barrier to the flow of solute and water between lumen and bath, and volume absorption is assumed to be driven exclusively by hydrostatic and osmotic pressure differences across this barrier. The model mimics the function of the tubule in two in vitro preparations: in simulations of the isolated tubule perfused under oil, the model correctly describes the solute concentration gradients that exist between the perfusate and absorbate and predicts differences in solute concentrations among absorbate droplets on the same tubule if luminal concentration becomes limiting. This prediction was tested experimentally with glucose and found to be correct. In simulations of the tubule perfused in an aqueous bath, the role of transmural hydrostatic pressure was explored; it is predicted that, at normal rates of in vitro perfusion (approximately 10 nl/min), increases in pressure have very little effect on volume absorption but can greatly alter the osmotic differences present across the wall of the tubule, especially with high values of osmotic water permeability. At high rates of perfusion, the ability of the tubule to produce a lumen hypotonic to the bath is reduced, but the direct effects of pressure on volume absorption become more apparent, resulting in relatively little effect of perfusion rate on volume absorption if the osmotic water permeability is sufficiently high. A similar relationship was seen experimentally. In all, this simple model provides a good prediction of function in isolated perfused tubules without any assumptions of hypertonic compartments within the epithelium.
Electrophysiological analysis of beta-receptor stimulation in salamander proximal tubules
Authors: Morgunov N. S.
Published: December 2017

Electrophysiological response to isoproterenol stimulation was studied in isolated perfused salamander proximal tubules. The addition of 10(-5) M isoproterenol to the bath superfusate depolarized both the cell membrane, and transepithelial potentials by 2.2 +/- 0.2 and 0.31 +/- 0.04 mV, respectively (P less than 0.01, n = 35) and significantly reduced the apical-to-basolateral membrane resistance ratio by 30% (P less than 0.01, n = 7) from a control value of 3.7 +/- 0.6. These responses were blocked by 10(-6) M propranolol but not mimicked by 10(-4) M adenosine 3',5'-cyclic monophosphate. Qualitatively similar effects were observed with 10(-3) and 10(-7) M isoproterenol. Further characterization of the 10(-5) M isoproterenol response revealed 1) a 50% reduction in the response following the removal of organic substrates from the luminal perfusate, 2) an absolute requirement for sodium, and 3) an absolute requirement for a functioning basolateral Na+-K+-ATPase. The data suggest that beta-receptor stimulation may increase sodium reabsorption by activating sodium cotransport systems.
Presence and possible role of a renal brush-border Gly-Pro-X-releasing exopeptidase
Authors: Andersen Knut-Jan , McDonald J. Ken
Published: December 2017

Differential pelleting of a rat renal cortical homogenate clearly demonstrated the microsomal localization of an N-terminal exopeptidase of the tripeptidyl peptidase (TPP) class that typically requires a free N-terminus to catalyze the release of collagen-related (Gly-Pro-X) “triplets” at pH 7.0 (TPP 7). Once fractionated by differential pelleting, microsomal populations of different size were subfractionated by equilibrium banding in sucrose gradients for the purpose of comparing the distribution profiles and the isopycnic banding densities of TPP 7 to those for known marker enzymes. This analytical approach permitted the localization of these enzymes to specific membrane domains in the renal cortex and provided evidence for the brush-border location of TPP 7. Notably, dipeptidyl peptidase IV (DPP IV), an established plasma membrane exopeptidase with a prolyl-bond specificity, gave banding densities and distributions that were consistent with the presence of both TPP 7 and DPP IV in the same membrane compartment. Because triplets of the Gly-Pro-X type released by TPP 7 would be ideal substrates for DPP IV, a coupled TPP 7-DPP IV exopeptidase mechanism at the luminal surface (brush border) of proximal tubule cells could therefore make a major contribution to the renal degradation and reabsorption of filtered collagen fragments.

tripeptidyl peptidase; aminopeptidase; collagen; rat kidney cortex

Submitted on February 11, 1987

Accepted on May 13, 1987
Sodium excretion in dogs with low-grade caval constriction: role of hepatic nerves
Authors: Levy M. , Wexler M. J.
Published: December 2017

Low-grade thoracic caval constriction will raise intrahepatic pressure without driving fluid from the vascular space as ascites. In eight such dogs where venous pressure was increased by 6.6 cmH2O, sodium balance studies showed a positive cumulative balance of 85 meq and a weight gain of 480 g over a 6-day period in the absence of any change in renal perfusion, glomerular filtration rate, central venous pressure, blood pressure, cardiac output peripheral vascular resistance, or plasma levels of aldosterone. Liver function tests, including bromosulfophthalein disappearance curves, were also normal. In dogs with either sham surgery, or subjected to equivalent venous hypertension of the abdominal vena cava or portal veins, there was a cumulative positive sodium balance of only 21–28 meq over a 2–day period. When the liver was completely denervated prior to performing the thoracic caval constriction, the sodium handling profile reverted to the same pattern as observed in sham controls, i.e., 22 meq cumulative sodium over a 3–day period. When the thoracic caval constriction was tightened to produce ascites, a LeVeen valve was inserted and the ascites mobilized. In response to 130 meq/day sodium diet, denervated dogs excreted the sodium load normally, whereas dogs with intact hepatic nerves retained sodium and developed anasarca. We conclude that intrahepatic baroreceptors may modulate sodium excretion in the presence of intrahepatic hypertension.
Effect of atrial natriuretic peptides on renal medullary solute gradients
Authors: Davis C. L. , Briggs J. P.
Published: December 2017

Studies were performed to examine the effect of the atrial natriuretic peptides on the solute gradient of the renal medulla. Experiments were performed in anesthetized male Sprague-Dawley rats given an infusion of either a purified atrial extract (n = 13), atrial natriuretic peptide 8–33 (1 microgram prime followed by 100 ng/min) (n = 8), furosemide (75 micrograms prime and 7.5 micrograms/min, n = 3), or vehicle alone (n = 17). Kidneys were removed 5 min after beginning the infusion, except in four animals, which were infused with atrial extract for 15 min before kidney removal. Both synthetic atrial peptides and an atrial extract result in rapid dissipation of the medullary gradient for urea, sodium, and total solute. No additional loss of solute was apparent at 15 min compared with 5 min. Furosemide caused equally rapid dissipation of the solute gradient at an approximately equidiuretic dose. The fall in tissue concentrations of urea and sodium was attributable to a loss of solute rather than addition of water. Administration of all three agents was associated with an increase in urinary urea excretion, which peaked earlier than the natriuresis. Urinary losses appear to account for a substantial portion of the loss of medullary solute.
Na-dependent effects of DOCA on cellular transport properties of CCDs from ADX rabbits
Authors: Sansom S. , Muto S. , Giebisch G.
Published: December 2017

Microelectrode methods were used to assess the Na-dependent effects of mineralocorticoids on the conductive transport properties of cortical collecting ducts (CCD) from adrenalectomized (ADX) rabbits. Rabbits were divided into four groups: control, 3 h treatment with deoxycorticosterone (DOCA), 18 h DOCA treatment, and 18 h DOCA plus amiloride treatment. After only 3 h of DOCA treatment the transepithelial potential (VT) increased significantly from -1.4 to -8.7 mV, and after 18 h VT increased further to -19.3 mV. The basolateral membrane potential (Vb) significantly increased after 18 h (from -61.6 to -87.6 mV). However, compared with treatment with DOCA alone for 18 h, both -VT and -Vb were significantly attenuated with DOCA plus amiloride treatment to -8.3 and -72.9 mV, respectively. The apical membrane Na and K currents (INaa and IKa) and conductances (GNaa and GKa) were all increased after 3 h DOCA treatment. After 18 h of DOCA treatment, IKa, INaa, and GKa increased further, but GNaa remained unchanged. On simultaneous treatment with DOCA and amiloride, the maximum pump current (Ipmax), IKa, INaa, and GKa but not GNaa were all reduced significantly. These results support a mechanism whereby mineralocorticoids first increase GNaa. A rise in cell Na results then in the simultaneous increase in GKa and sodium transport, probably by insertion of new Na pumps. An additional direct effect of DOCA on GKa and Ipmax is not excluded.
Transport of tetraethylammonium by rabbit renal brush-border and basolateral membrane vesicles
Authors: Wright S. H. , Wunz T. M.
Published: December 2017

Brush-border and basolateral membrane vesicles (BBMV and BLMV, respectively) from rabbit renal cortex were used to study transport of the organic cation, tetraethylammonium (TEA). Outwardly directed proton gradients stimulated uptake of TEA into BBMV and supported concentrative accumulation. Furthermore, an inwardly directed H+ gradient accelerated TEA efflux from BBMV. These data suggest that TEA transport in BBMV involved exchange with H+. The Jmax and Kt for TEA transport into BBMV under pH equilibrium conditions (pH 7.5) were 2.1 nmol.mg-1.min-1 and 0.15 mM, respectively. Under pH gradient conditions (6.0in:7.5out), Jmax increased by 270% with no effect on Kt. Uptake of TEA into BBMV was stimulated by an inside-positive electrical potential difference (PD), although exchange of TEA for H+ appeared to be one for one. In BLMV, H+ gradients had little effect on TEA uptake and were incapable of supporting concentrative transport. The Jmax and Kt for TEA transport in BLMV were 0.33 nmol.mg-1.min-1 and 0.37 mM, respectively. Inside-negative PDs stimulated this uptake, suggesting that it involved an electrically conductive pathway. TEA transport in BBMV and BLMV was inhibited by amiloride and cimetidine, although p-aminohippuric acid was without effect. Thus, secretion of TEA involves carrier-mediated transport steps at both the luminal and peritubular membranes, although an active step is not evident in isolated BLMV.
Bicarbonate transport in collecting tubules from outer stripe of outer medulla of rabbit kidneys
Authors: McKinney T. D. , Davidson K. K.
Published: December 2017

The purpose of this study is to characterize the features of bicarbonate (total CO2) transport in isolated perfused collecting tubules obtained from the outer stripe of the outer medulla (OMCTos) of rabbit kidneys. Under control conditions (25 mM HCO3- in the perfusate and bath), all OMCTos studied absorbed total CO2 at a mean rate of 8.61 +/- 0.44 pmol.mm-1.min-1. Ouabain (10(-4) M in the bath) did not affect the rate of total CO2 absorption (JtCO2). Addition of the diethylstilbene 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a concentration of 10(-4) M or replacement of bath chloride by gluconate reduced JtCO2 by approximately 50%, whereas replacement of luminal chloride increased JtCO2 by 40%. The carbonic anhydrase inhibitors acetazolamide and ethoxyzolamide in concentrations of 10(-4) M had little effect on JtCO2. In a concentration of 10(-3) M, acetazolamide reduced JtCO2 by only 31%. OMCTos obtained from rabbits with ammonium chloride-induced metabolic acidosis did not have increased rates of total CO2 absorption compared with the control, but treatment of animals with mineralocorticoids increased JtCO2. These results indicate that OMCTos are capable of significant bicarbonate absorption in vitro. This absorption 1) is independent of sodium transport, 2) appears to require, at least in large part, HCO3- or OH- -Cl- exchange across the basolateral cell membrane of acid-secreting cells, 3) is much more resistant to inhibition by carbonic anhydrase inhibitors than reported previously for other rabbit nephron segments, and 4) is stimulated by prior mineralocorticoid treatment of animals but not by prior metabolic acidosis in vivo.
Na+-H+ antiporter in posthypercapnic state
Authors: Yang W. C. , Arruda J. A. , Talor Z.
Published: December 2017

Posthypercapnic metabolic alkalosis has been attributed to decreased HCO3 excretion because of low glomerular filtration rate (GFR), volume contraction, or chloride depletion. We have previously shown that chronic hypercapnia enhances the Vmax of the Na+-H+ antiporter. We reasoned that an increased Vmax of the Na+-H+ antiporter could play a role in the maintenance of posthypercapnic metabolic alkalosis. To test this hypothesis, we measured the kinetics of the Na+-H+ antiporter by the dissipation of the quenching of acridine orange fluorescence in purified brush-border membrane obtained from posthypercapnic rabbits. The kinetic parameters were measured in controls and in rabbits that were exposed to hypercapnia for 48 h and then allowed to breathe room air for 3, 24, or 48 h. In luminal membranes prepared from posthypercapnic animals, the Vmax of the Na+-H+ antiporter was significantly increased after 3 and 24 h but not after 48 h compared with controls. The increase in Vmax was not different from that of hypercapnic animals. There was no difference in the Km of the Na+-H+ antiporter among these five groups. Amiloride inhibited the Vmax equally in membranes from control and posthypercapnic rabbits. Proton permeability was comparable among the groups. These data indicate that the increase in Vmax in posthypercapnic rabbits is mediated through the electroneutral Na+-H+ exchange and not through conductive H+ and Na+ pathway. Glucose uptake was not different in control and posthypercapnia, indicating a selective increase in Na+-H+ antiporter activity. At 3 and 24 h posthypercapnia, HCO3 concentration was higher than control.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of indomethacin on renal response to atrial natriuretic peptide
Authors: Gaillard C. A. , Koomans H. A. , Rabelink A. J. , Mees E. J.
Published: December 2017

We studied the effect of alpha-human natriuretic peptide (ANP, 100 micrograms iv) on renal sodium handling in eight healthy subjects before and after 7 days of indomethacin (50 mg 3 times a day). Sodium intake was 100 mmol/day. Prior to indomethacin, ANP caused a fourfold rise in sodium excretion over the first 20 min and a threefold rise in fractional sodium excretion. The clearance studies, performed during maximal water diuresis, showed increased fractional free water clearance and lithium clearance. Indomethacin caused marked sodium retention. Complete escape did not occur until the sixth day, when cumulative balance was 244 mmol (range 176-337). By this time renin and aldosterone were suppressed and fractional lithium and free water clearance reduced. The natriuretic effect of ANP was not attenuated, and the fractional excretion of sodium and chloride rose even more than without indomethacin. The reduction in lithium and free water clearance under indomethacin tended to be reversed by ANP. These data suggest that the natriuretic effect of ANP is not mediated by or dependent on renal prostaglandins. Indomethacin and ANP appear to have opposite effects on sodium excretion, maximal free water clearance, and lithium clearance.
Electrolyte transport in a central core model of the renal medulla
Authors: Stephenson J. L. , Zhang Y. , Eftekhari A. , Tewarson R.
Published: December 2017

Transport of Na+, K+, Cl-, urea, and water is described in a central core model of the renal medulla. Equations for mass balance, Poiseuille flow, and the Nernst-Planck equation describe the continuous behavior of the system along the medullary axis and along the distal nephron; the Kedem and Katchalsky phenomenology describes passive transmural transport; active transmural transport obeys Michaelis-Menten kinetics. Numerical solution of the differential equations shows that to a close approximation any combination of active Na+ and active Cl- transport can generate the same concentration profiles but will generate very different potential profiles, and consequently, very different K+ absorption in thick ascending limb of Henle's loop. If a net transport stoichiometry of 2 Cl- ions to 1 Na+ ion is selected for the pumps, an active Cl- transport rate of approximately 10,000 peq.s-1.cm-2 gives K+ and Na+ concentrations in early distal nephron and a medullary osmolality profile in reasonable agreement with experimental data.
The contribution of atrial natriuretic factor to acute volume natriuresis in rats
Authors: Barbee R. W. , Trippodo N. C.
Published: December 2017

To explore the role of atrial natriuretic factor (ANF) in acute volume-expansion natriuresis, right atrial pressure (RAP), mean arterial pressure (MAP), rate of urinary sodium excretion (UNaV), and plasma immunoreactive ANF (IR-ANF) were measured in anesthetized, open-chest rats. All groups received 33% blood volume expansion with whole blood in 15 min. RAP was not allowed to increase in one group by using a caval snare. MAP was controlled in a second group with the use of an aortic snare. A third group (RAP-controlled ANF) with control of RAP received rat ANF (99-126) at doses designed to mimic the IR-ANF measured in the MAP-controlled rats. IR-ANF was similar 5 min after blood infusion in rats exhibiting increased RAP (490 +/- 111 pg/ml) and in those without increased RAP but receiving ANF infusion (447 +/- 44 pg/ml); this was also true at 45 min after blood infusion (232 +/- 44 vs. 263 +/- 27 pg/ml). IR-ANF in rats with constant RAP (without ANF infusion) remained low throughout the experiment (61 +/- 10 and 74 +/- 10 pg/ml). UNaV increased only in the MAP-controlled and ANF-infused groups, but peak responses occurred 15-30 min after the onset of volume expansion in the former, and 60-75 min in the latter. Thus, factors other than ANF mostly accounted for the immediate natriuresis after volume expansion, whereas ANF predominated after a delayed period. The results suggest that increased plasma ANF accounted for at least 34% of the observed natriuretic response to acute volume expansion in anesthetized rats.
Calcium antagonists preferentially dilate preglomerular vessels of hydronephrotic kidney
Authors: Fleming J. T. , Parekh N. , Steinhausen M.
Published: December 2017

The hydronephrotic kidney of Inactin-anesthetized female Wistar rats was exteriorized in a controlled bath to directly observe preglomerular and postglomerular vessels via television microscopy. Nitrendipine, added to the bath in a concentration that did not alter blood pressure, induced a concentration-dependent dilation of preglomerular vessels. The arcuate artery maximally dilated by 29 +/- 4%, the interlobular artery by 24 +/- 5%, the afferent arteriole near the interlobular artery by 60 +/- 9%, and near the glomerulus by 28 +/- 13%. In contrast the efferent arteriole near the glomerulus dilated by only 11 +/- 6% and near the welling point by 7 +/- 9%. Similarly, diltiazem significantly dilated preglomerular vessels but not efferent arterioles. Acetylcholine significantly dilated all preglomerular vessels and dilated the afferent arterioles near the glomerulus (by 51 +/- 8%) to a greater extent than the calcium blockers. Acetylcholine also significantly dilated the efferent arterioles (near the glomerulus by 26 +/- 5% and near the welling point by 12 +/- 3%). These data suggest that the tone of the preglomerular vessels of the hydronephrotic kidney is more dependent on the entry of extracellular calcium through calcium antagonist-sensitive channels (i.e., potential dependent) than is the tone of the afferent arterioles near the glomerulus and the efferent arterioles.
Kaliuretic regulatory factors in the rat
Authors: Rutledge J. C. , Rabinowitz L.
Published: December 2017

To evaluate the role of aldosterone, plasma potassium, and sodium and urine excretion rates in controlling both total daily potassium excretion and the diurnal cyclic excretion of potassium, we performed experiments on unanesthetized, undisturbed rats kept in a 12-h light/12-h dark environment and fed a liquid diet. Independent variations were imposed on potassium intake, sodium intake, and, in groups of adrenalectomized rats, on aldosterone infusion rates. Potassium intake was 2.6, 10.6, and 18.7 meq/day. Sodium intake was 2.1, 6.7, and 17 meq/day. Aldosterone infusion was 0.1, 0.4, 1, and 10 times a basal rate of 1 microgram.day-1.100 g-1, with constant dexamethasone infusion at 1.43 micrograms.day-1.100 g-1. Twenty-four-hour excretion of potassium and sodium balanced 24-h intake of potassium and sodium regardless of the imposed combination of known regulatory factors. The amplitudes of potassium and sodium excretion during the diurnal cycle were each closely related to the ongoing levels of potassium and sodium intake. Plasma potassium was measured at the peak of the potassium cycle. It is suggested, based on analysis of the results, that when caloric balance was maintained, the amplitude of the diurnal potassium cycle was not importantly influenced by the rates of sodium and urine excretion, and, in addition to effects of aldosterone and plasma potassium concentration, the amplitude was importantly influenced by unspecified, homeostatically effective kaliuretic factors. Adrenalectomized rats receiving subbasal aldosterone replacement rejected the high potassium diet, were anuric, lost weight, and were severely hyperkalemic, observations indicating the necessity of adequate aldosterone for maintenance of potassium homeostasis.
Stretch-activated potassium channels in renal proximal tubule
Authors: Sackin H.
Published: December 2017

A short open-time potassium (K) channel that has previously been identified in the basolateral membrane of Necturus proximal tubule (17) is activated by membrane stretch. Application of between 12 and 20 cmH2O negative pressure to the patch pipette reversibly increases mean number of open basolateral K channels (NP0) by a factor of 5.3 +/- 2 in cell-attached patches (n = 4) and a factor of 13.7 +/- 5 in excised patches (n = 8). This stretch activation does not alter channel selectivity or conductance and depends on neither the direction of K current nor the orientation of the patch ("inside-out" vs. "outside-out"). The increase in NP0 occurs within seconds after applying negative pressure to the patch and is proportional to applied negative pressure. Stretch activation of the basolateral potassium channel may play an important role in proximal tubule cell volume regulation. For example, if swelling stretches the basolateral membrane, the resulting increase in NP0 could restore cell volume by loss of K (with an accompanying anion) followed by osmotic exit of water.
The collecting tubule of Amphiuma. I. Electrophysiological characterization
Authors: Hunter M. , Horisberger J. D. , Stanton B. , Giebisch G.
Published: December 2017

Single collecting tubules of Amphiuma kidneys were perfused in vitro to characterize their electrophysiological properties. The lumen-negative potential (-24 mV) was abolished by amiloride in the lumen and by ouabain in the bath. Ion substitution experiments in the lumen demonstrated the presence of a large sodium conductance in the apical cell membrane, but no evidence was obtained for a significant potassium or chloride conductance. Ion substitutions in the bath solution and the depolarizing effect of barium on the basolateral membrane potential demonstrated the presence of a large potassium conductance in the basolateral cell membrane. Measurements of dilution potentials in amiloride-treated tubules revealed a modest cation selectivity of the paracellular pathway. These results support a cell model in which sodium reabsorption occurs by electrodiffusion across the apical cell membrane and active transport across the basolateral cell membrane. The absence of a detectable potassium conductance in the apical cell membrane suggests that secretion of this ion cannot take place by diffusion from cell to lumen.