bluuebunny/crossref_metadata_2025 huggingface dataset:
Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog
Authors: Bell P. D. , Thomas C. , Williams R. H. , Navar L. G.
Published: December 2017

Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.
Effect of magnesium on sodium transport in toad urinary bladder
Authors: Aguilera A. J. , Kirk K. L. , DiBona G. F.
Published: December 2017

Voltage-clamp techniques were employed to examine the effect of magnesium (Mg) on sodium transport in the isolated urinary bladder of the Dominican toad. Substitution of 1 mM Mg had no effect, but 3-mM Mg substitution resulted in a reversible increase in short-circuit current (27%) and potential difference (19%) and decrease in transepithelial resistance (14%); no greater effect was seen with 5- or 10-mM Mg substitution. The effect was produced by mucosal or mucosal and serosal Mg substitution; serosal Mg substitution was without effect. Analysis of electrical parameters disclosed that magnesium increased net sodium transport via an effect on the sodium pump.
Intracellular activities of sodium and potassium
Authors: Civan M. M.
Published: December 2017

The intracellular contents of Na+ and K+ appear to modulate a variety of cellular and tissue functions, including transepithelial transport. However these total ionic contents appear to consist of heterogeneous populations of Na+ and K+. No more than a few percent of intracellular Na+ and K+ appear bound. Thus, the heterogeneity of the intracellular ionic contents must reflect subcellular compartmentalization. Recent technical advances in the preparation and use of ion-selective microelectrodes have permitted progress in defining the possible sites of such intracellular compartmentalization. Furthermore, intracellular recording with microelectrodes and micropipettes now provides a technique with which to directly monitor the chemical activities of Na+ and K+ within the cytoplasm as a function of the state of transepithelial transport. This approach has already provided information necessitating a reexamination of certain classical concepts of transport physiology.
Contamination of prolactin preparations by antidiuretic hormone and oxytocin
Authors: Vorherr H. , Vorherr U. F. , Solomon S.
Published: December 2017

Since impurities consisting of neurohypophysical hormones in prolactin powder may be responsible for the vascular and renal effects attributed to prolactin, rat (NIH-RP-1), ovine (NIH-P-S-10, S-12), and bovine (NIH-P-B4) prolactin preparations were examined for their content of ADH and oxytocin by rat antidiuresis, milk-ejection, and blood pressure assays. Activities were identified as due to ADH or oxytocin by incubation of prolactin solutions with antisera against ADH, oxytocin, and prolactin, or with pregnancy plasma. The ADH content of rat, ovine (P-S-10, P-S-12) and bovine prolactin was found to be 104.5 +/- 7.1 (means +/- SE), 2.5 +/- 0.2, 1.6 +/- 0.1, and 1.6 +/- 0.5 mU/mg powder, respectively; the corresponding values for oxytocin content were 155.3 +/- 3.5, 1.2 +/- 0.1, 0.5 +/- 0.1, and 1.2 +/- 0.01 mU/mg powder, respectively. Because antidiuretic, milk-ejection, and blood pressure activities of the various prolactins were eliminated after incubation with antisera against ADH and oxytocin, or with pregnancy plasma, but not with prolactin antisera, it is concluded that the reported vascular and renal prolactin effects are attributable to ADH contamination of the prolactin preparation rather than to the prolactin molecule itself. These findings have implications for renal and vascular prolactin research.
Renal potassium excretion in sheep during sodium sulfate, phosphate, and chloride infusion
Authors: Rabinowitz L. , Gunther R. A.
Published: December 2017

The renal excretion of potassium by unanesthetized sheep was studied in clearance studies in which water and sodium excretion were elevated by intravenous infusion of isotonic sodium chloride, hypertonic sodium phosphate, or hypertonic sodium sulfate. Aldosterone was infused at 10 microgram/h in some experiments with sodium sulfate. Sodium excretion increased in all experiments, rising at times to equal 25% of the filtered load. Urine flow increased in most experiments. Glomerular filtration rate increased only with infusion of isotonic saline. No consistent change in potassium excretion occurred under any of these loading conditions. This finding contrasts with the increase in potassium excretion commonly seen in man, dogs, and rats intravenously loaded with sodium salts.
Renal sugar transport in the winter flounder: V. secretion of 2-deoxy-D-galactose
Authors: Pritchard J. B. , Booz G. , Kleinzeller A.
Published: December 2017

Isolated renal tubules and renal clearance techniques were used to characterize the renal handling of 2-deoxy-D-galactose (2-d-Gal) by the winter flounder (Pseudopleuronectes americanus). In vitro, energy-dependent, pH-sensitive uptake of 2-d-Gal (2–100 micron) was seen at the antiluminal face of the cell. Clearance measurements showed net secretion of 2-d-Gal in vivo. The mean clearance of 2-d-Gal in 18 fish was 0.98 +/- 0.16 ml/h while the glomerular filtration rate (GFR) was only 0.37 +/- 0.10 ml/h. Secretion was associated with marked renal accumulation of both 2-d-Gal and phosphorylated derivatives (2-d-Gal-1-phosphate). Tissue-to-plasma ratios (T/P) averaged 19 for free sugar and 59 for total sugar. Both clearance ratio and T/P were reduced to approximately 1 by injection of galactose (2.5 mmol/kg) simultaneously with 2-d-Gal (25 mumol/kg). Phlorizin (2.5 mumol/kg) increased net 2-d-Gal secretion, whereas glucose (2.5 mmol/kg) produced no change in secretion. Both compounds depressed 2-d-Gal T/P. This result suggests the presence of readsorptive transport at the brush border, sensitive to glucose and phlorizin.
Renin secretion as a function of renal renin content in dogs
Authors: Park C. S. , Malvin R. L. , Murray R. D. , Cho K. W.
Published: December 2017

The in vivo and in vitro rates of renin secretion were measured in kidneys from five groups of dogs in which renal perfusion pressure, salt diet, and neural input were varied to cause large changes in renin secretion rates and renal renin content. It was found that both the in vivo and in vitro secretory rates were proportional to the renal renin content. However, in vitro secretion rates were dependent on content up to 100 ng angiotensin I/mg tissue per h. At higher renin contents no increment in in vitro secretion rate was seen. In vivo secretion rate did not appear to reach a maximum until renal renin content was above 250 ng AI/mg tissue per h. The data are interpreted to support the hypothesis that there exist at least two pools of renin. One releases renin at a fractional rate of about 1.5% of the total content per hour. The other releases renin at a rate dependent on the magnitude of the stimuli acting on the kidneys. It is also suggested that the rate of renin synthesis may be a determinant of the basla rate of renin secretion.
Inhibition of renin release from rat kidney slices by the angiotensins
Authors: Naftilan A. J. , Oparil S.
Published: December 2017

The mechanism and structural basis of the inhibition of renin release by angiotensin II (AII) were studied in rat kidney slices. Renin release was inhibited by AII and the (2–8), (3–8), (4–8), and (5–8) peptides of AII (5 X 10(-5) M). These constituent peptides of AII which share a common carboxyl terminus inhibited renin release with a sharp decrease in potency when the amino-terminal amino acid was removed. Saralasin attenuated the inhibition of renin release induced by equimolar concentrations of AII. Dose-response curves for AII and the (2–8) peptide [angiotensin III (AIII)] indicate that AII is a more potent inhibitor of renin release than is AIII. Depletion of renal norepinephrine by reserpine (10 mg/kg, i.p.) or pretreatment of slices with papaverine (1 X 10(-4) M) did not block the action of AII. The data give evidence for a direct action of AII on the juxtaglomerular cells independent of an interaction with either the sympathetic nervous system or the arteriolar baroreceptor and suggest that the intrarenal receptors that mediate AII-induced inhibition of renin release differ from AII receptors in the adrenal cortex.
H + transport in urinary epithelia
Authors: Al-Awqati Q.
Published: December 2017

This review of urinary acidification is primarily based on studies in isolated epithelia such as the turtle bladder. Despite the lack of unambiguous proof, the wealth of indirect evidence suggests that the cause of bicarbonate absorption is H+ secretion into the lumen. The mechanisms that regulate H+ transport are discussed. The electrochemical gradient for protons across the membrane is found to be the most fundamental regulator not only of passive movement but also of active transport. CO2 and aldosterone stimulate H+ transport, the latter by a mechanism apparently separate from the effect of this hormone on sodium transport. Although carbonic anhydrase activity is important for optimal function of the H+ pump, the results with carbonic anhydrase inhibitors need to be interpreted with caution. The evidence for Na:H exchange is reviewed and found to be not very persuasive, The metabolic pathways that fuel H+ transport are found to be all the major energy-yielding reactions in the cell, but particular prominence is given to the new discovery of the role of the pentose shunt in energizing transport. Finally, I discuss the important role H+ transport in energy transduction in subcellular organelles.
Extracellular water measurements: organ tracer kinetics of bromide and sucrose in rats and man
Authors: Pierson R. N. , Price D. C. , Wang J. , Jain R. K.
Published: December 2017

Bromide and sucrose distributions were measured as functions of time after tracer injection into 14 rat organs that accounted for 93% of body wt, with the goal of evaluating the use of bromide and sucrose as tracers for the extracellular water volume (ECW). The tracers, Na, 82Br, 125I-labeled human serum albumin, [14C]sucrose, and 3H2O, were used to calculate bromide and sucrose content in red cells, plasma, and 13 blood-free organs. Selective concentration of Br- occurs in RBC, stomach, and skin, accounting in part for the discrepancy between the Br- space and the smaller ECW volume as derived from other methods. Sucrose is rapidly metabolized in the rat and its 14C tracer cannot be used for ECW determination in this species. The kinetics of Br- distribution were estimated in rats and in 16 human subjects by measuring plasma disappearance values and specific organ uptakes. A pharmacokinetic compartmental model was derived, containing explicit parameters for blood flow, diffusion constants, and ECW spaces separately for each organ. Precise fitting of experimental bromide data was achieved for the rat; satisfactory fitting was also achieved in man from more limited plasma and biopsy data.
Glucose-mediated inhibition of phosphate reabsorption in rat kidney
Authors: Corman B. , Touvay C. , Poujeol P. , de Rouffignac C.
Published: December 2017

Clearance, tracer intra-arterial injection, and tracer intratubular microinjection techniques were used on two strains of Wistar rats. In Saclay rats, clearance studies during hyperphosphatemia showed that glucose significantly decreased reabsorption of phosphate; during normal phosphatemia, glucose induced a 25% inhibition both in nondiuretic and in volume-expanded animals; thyroparathyroidectomy did not modify this inhibition. When mannitol was substituted for glucose, no change in phosphate reabsorption was noted. Tracer injection into the renal arteries of [3H]inulin, [14C]glucose, and [32P]-phosphate with or without additional unlabeled glucose or mannitol showed that the presence of glucose significantly increased 14C and 32P urinary recoveries but not mannitol. Intratubular paired microinjections into early proximal tubules of the same tracers with and without glucose showed that addition of sugar also increased the 14C and 32P urinary recoveries. In Munich rats, the effects were much less marked than in Saclay rats. It is concluded that the inhibitory effect of glucose 1) partly results from intrarenal factors, 2) is linked to glucose reabsorption per se but not to a nonspecific osmotic intraluminal effect, 3) is localized on the tubular luminal side, and 4) is subject to strain differences.
Cross-circulation study of natriuretic factors in rats with reduced nephron mass
Authors: Wilson D. R. , Honrath U.
Published: December 2017

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2–3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.
A network thermodynamic model of salt and water flow across the kidney proximal tubule
Authors: Thomas S. R. , Mikulecky D. C.
Published: December 2017

This network thermodynamic model of kidney proximal tubule epithelium treats coupled salt and water flow across each component membrane of the epithelium. We investigate the effects of various relative internal parameter values on the concentration of transepithelial flow, the concentrations in the cell and interspace, and the distribution of flows between cellular and paracellular routes. Best fit is obtaine if the apical and basolateral membrane reflection coefficients (or) are equal. The measured transepithelial filtration coefficient, Lp, is a function not only of the component Lps but also of the internal concentrations, or's, and permeabilities. For the given system topology (i.e., connectedness), parameters of component membranes must be within a narrow range to be consistent with experimental results. The dependence of the concentration of transported fluid on the balance between the solute pump rate and the transepithelial volume flow driving force is shown. This has implications for the effects of peritubular or lumen oncotic pressure on salt and water flow. With Appendix B of this paper and a user's guide for a circuit-simulation package (e.g., SPICE or PCAP) the reader can perform similar network analyses of transport models himself.
Sodium-coupled chloride transport by epithelial tissues
Authors: Frizzell R. A. , Field M. , Schultz S. G.
Published: December 2017

There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in "leaky" or "moderately leaky" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented.
Local intrarenal vasoconstrictor-vasodilator interactions in mild partial ureteral obstruction
Authors: Ichikawa I. , Brenner B. M.
Published: December 2017

Micropuncture studies were performed in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values for superficial single nephron (SN)GFR, total GFR, and initial glomerular plasma flow rate (QA) in obstructed kidneys were essentially identical to values in nonobstructed kidneys. Nevertheless, glomerular capillary hydraulic pressure (PGC) was significantly higher in obstructed than in nonobstructed kidneys. This increase in PGC served to offset the markedly reduced glomerular capillary ultrafiltration coefficient that was also confined to the kidneys ipsilateral to the ureteral obstruction. During infusion of indomethacin or meclofenamate, SNGFR and QA decreased significantly, in association with elevations in arteriolar resistances in obstructed kidneys, whereas such changes were not observed in nonobstructed kidneys. The results suggest that local intrarenal factors, rather than circulating or systemic factor(s), bring about functional adaptations to partial ureteral obstruction. In particular, an indomethacin- and meclofenamate-sensitive vasodilator (presumably prostaglandin) plays a role in antagonizing the effects of a simultaneously acting vasoconstrictor which, although not identified, displayed the functional properties of angiotensin II.
Active amino acid absorption by proximal convoluted and proximal straight tubules
Authors: Barfuss D. W. , Schafer J. A.
Published: December 2017

Transport of glycine and alpha-aminoisobutyric acid (AIB) was studied in proximal convoluted (PCT) and proximal straight (PST) tubules isolated from rabbit kidney. In both segments, unidirectional lumen-to-bath fluxes (J1 leads to b) (pmol min-1mm-1) of glycine and AIB exceeded corresponding bath-to-lumen fluxes (Jb leads to 1), which demonstrated that both were actively absorbed. During J1 leads to b measurements, intracellular concentrations of both amino acids were greater than the luminal concentration, indicating that the site of active transport was the luminal membrane. Replacement of Na+ by choline in both perfusate and bath (PCT) or perfusate alone (PST) reduced J1 leads to b for glycine to equal Jb leads to 1. Nonlinear fitting of the relationship between J1 leads to b and the mean luminal glycine concentration according to Michaelis-Menten kinetics gave Jmax values of 28.5 (PCT) and 2.5 (PST) pmol min-1 mm-1, and Km values of 11.8 (PCT) and 0.7 (PST) mM. There was a parallel, Na+-independent, nonsaturable component of J1 leads to b characterized by an apparent permeability coefficient of 0.19 micron/s in the PCT and 0.04 micron/s in the PST.
The use of linear nonequilibrium thermodynamics in the study of renal physiology
Authors: Essig A. , Caplan S. R.
Published: December 2017

Classical formulations for the analysis of membrane transport processes, which ignored possible interactions between flows of diverse permeant species, often led to inconsistencies in the evaluation of permeability coefficients. For water flow induced by an osmotic pressure difference this difficulty was resolved by Staverman's introduction of the reflection coefficient sigma, a parameter which incorporates the interaction between solute and solvent in the course of their passage through a membrane. A comprehensive nonequilibrium thermodynamic (NET) formalism suitable for many biological systems was provided by Kedem and Katchalsky. For an n-flow system each flow is in general dependent on n forces; the assumption of Onsager reciprocity, however, reduces the number of independent phenomenological coefficients. Although NET is widely applied in the study of renal physiology, fundamental theoretical and practical problems remain. Basic considerations are the need to control or evaluate the influence of all coupled flows and to establish conditions fostering linear dependencies of flows on forces. When this is done a transport system may be characterized in terms of intrinsic membrane parameters, facilitating the systematic study of the effects of drugs, hormones, and various experimental perturbations.
Relationship between arterial and cisternal CSF oxygen tension in rabbits
Authors: Jankowska L. , Grieb P.
Published: December 2017

Oxygen tension was measured in samples of blood and cisternal cerebrospinal fluid taken from anesthetized, paralyzed, and mechanically ventilated rabbits at various levels of arterial PO2. Cerebrospinal fluid oxygen tension (CSF PO2) was correlated with arterial PO2 (linear regression equation PCSFO2 = 0.2472 Pao2 + 42.34). During hypoxia CSF PO2 was higher than arterial PO2 in most experiments. These data can be attributed to the Bohr effect, which would increase the PO2 of the blood in choroid plexus capillaries as a result of its acidification. The acidification was suggested by Maren (Am. J. Physiol. 222: 885-889, 1972) to be a part of the ionic exchanges involved in cerebrospinal fluid formation. Such a mechanism may be of importance for supporting choroid plexus metabolism and function during hypoxia. This mechanism is most clearly seen in the rabbit.
Effects of inhibitors in lumen on PAH and urate transport by isolated renal tubules
Authors: Dantzler W. H. , Bentley S. K.
Published: December 2017

Effects of the presence of unlabeled p-aminohippurate (PAH) or urate, probenecid, and phenol red in the lumen on labeled PAH or urate transport by isolated, perfused snake (Thamnophis spp.) proximal renal tubules were studied. Net secretion of labeled urate and luminal membrane permeability to urate were unaffected by the presence of unlabeled urate (up to 0.1 mM) or probenecid (up to 1.0 mM) in lumen only. The data are compatible with movement of urate from cells to lumen during urate secretion by a simple passive process. Net secretion of labeled PAH was rapidly and reversibly depressed to about 25-35% of control when unlabeled PAH (0.05 mM), phenol red (0.05 mM), or probenecid (0.1 mM) was added to the lumen only. During maximum depression of PAH transport, luminal membrane permeability to PAH was reduced by 60-70%. The data suggest that movement of PAH from cells to lumen down an electrochemical gradient during PAH secretion occurs by a readily inhibited, mediated process.
Selective effects of bumetanide on chloride transport in bullfrog cornea
Authors: Candia O. A. , Schoen H. F.
Published: December 2017

Page F297: O. A. Candia and H. F. Schoen. “Selective effects of bumetanide on chloride transport in bullfrog cornea.”The values for oxygen consumption (means ± SE) as given in the abstract and in Table 4 are 100 times larger than the correct values. In the abstract, line 6 from the bottom should read “from 3.52 ± 0.14 to 2.97 ± 0.19 μl/h ·cm2.” Table 4 (page F300) should be

(See PDF)
Resistance to the phosphaturic effect of parathyroid hormone in the hamster
Authors: Harris C. A. , Seely J. F.
Published: December 2017

The renal effects of parathyroid hormone (PTH) and dibutyryl 3'5'-cyclic AMP (DBcAMP) were studied in thyroparathyroidectomized hamsters. The hamsters were permitted free access to food and water or fasted for 16 h. PTH caused a phosphaturia in the fed hamster (fractional excretion of phosphate (FEPO4) increased from 5.8 +/- 1.3 to 27.4 +/- 4.6%, P less than 0.001) but not in the fasted hamster (from 9.9 +/- 2.5 to 12.4 +/- 2.5%, NS), whereas calcium excretion decreased significantly in both groups. There was no significant difference in blood acid-base or phosphate levels between the two groups. Insulin did not restore the phosphaturic response to PTH (FEPO4 from 7.7 +/- 2.6 to 5.3 +/- 1.7%), whereas phosphate or NH4Cl infusion did, FEPO4 increasing from 20.9 +/- 3.1 to 38.1 +/- 5.4% (P less than 0.02) and from 19.5 +/- 3.8 to 39.0 +/- 7.5%, respectively. DBcAMP caused a phosphaturia both in the fasted (from 9.6 +/- 2.7 to 20.1 +/- 4.5%, P less than 0.01) and fed (from 2.5 +/- 0.5 to 10.7 +/- 1.5%, P less than 0.02) hamster. A fasting state of up to 64 h did not produce resistance to PTH in the rat. It is concluded that fasting produces resistance to the phosphaturic but not the calcium-retaining effects of PTH in the hamster. The resistance may occur, at least partly, prior to the production of cAMP within the renal tubular cell.
Questions and replies: role of the collecting tubule in fluid, sodium, and potassium balance
Authors: Jamison R. L. , Sonnenberg H. , Stein J. H.
Published: December 2017

In terms of day-to-day regulation of fluid and electrolyte balance, the collecting tubule system appears to occupy a paramount position among segments of the renal tubule. Controversy has arisen concerning the quantitative contribution by the collecting tubule system to the regulation of individual solute excretion, which in part may be due to differences among the investigative techniques employed. In this Editorial Review, R. L. Jamison summarizes current views on the function of the collecting tubule system, particularly with regard to regulation of sodium and potassium excretion, and then poses seven questions pertaining to this topic. H. Sonnenberg, who has revived the microcatheterization technique, and J. H. Stein, whose group has employed the micropuncture method, respond to these questions. The key issues addressed are: 1) the principal factors that influence transtubular movement of sodium and potassium across the collecting tubule; 2) the limitations and potential artifacts of the microcatheterization and micropuncture techniques when used to examine the function of the collecting tubule; 3) apparent discrepancies among results obtained by micropuncture in vivo, microcatheterization in vivo, and microperfusion in vitro of the collecting tubule; and 4) major unresolved questions concerning the function of the collecting tubule.
Denervated and intact kidney responses to saline load in awake and anesthetized dogs
Authors: Sadowski J. , Kurkus J. , Gellert R.
Published: December 2017

The function of the innervated and denervated kidney was examined in clearance studies with unilaterally renal-denervated conscious and anesthetized dogs before and after saline loading. Barbiturate anesthesia distinctly depressed hemodynamics and excretory function of both kidneys and increased the difference between the denervated and innervated organ. In conscious moderately hydrated dogs the denervated kidney excreted slightly more sodium and water, while after saline loading higher excretion was observed on the innervated side. The denervated-to-innervated kidney ratios for UNaV, UNaV/100 ml GFR, and urine flow fell significantly from mean control values of 1.27, 1.27, and 1.20, respectively, to 0.80, 0.87, and 0.77 after extracellular volume expansion. Similar alterations of the ratios were observed in anesthetized dogs, but higher excretion of the denervated kidney persisted after saline loading. It is concluded that the greater natriuretic response of the intact kidney to saline infusion was due to inhibition of sodium-retaining action of renal efferent nerve activity by acute extracellular volume expansion.
Transtubular leakage of glomerular filtrate in human acute renal failure
Authors: Myers B. D. , Chui F. , Hilberman M. , Michaels A. S.
Published: December 2017

Ten postcardiac surgical patients with acute renal failure (ARF) were infused with inulin and dextran 40. Plasma and urine were then submitted to gel-permeation chromatography to ascertain the apparent fractional clearance profile for the dextrans. Compared to normal volunteer controls, the fractional clearance profile was substantially elevated for dextran molecules in the Einstein-Stokes radius (r) range 20-40 A. For the smaller molecules (r = 20-28 A), fractional dextran clearance in ARF was frequently in excess of unity. A simple mass conservation model which assumes that the "true" fractional dextran clearance profile for the glomerulus (in Bowman's space) in ARF is the same as that for normal controls, when applied to the experimental observations, revealed that in ARF, on the average, 50% of filtered inulin is lost by tubular backleakage. Furthermore, the model permitted an estimate of the permeability properties of the damaged tubular wall. This indicated tubular permeability not unlike that of the normal glomerulus to dextran molecules with r less than 30 A, but relative impermeability to larger dextran molecules.
Theoretical model for glomerular filtration of charged solutes
Authors: Deen W. M. , Satvat B. , Jamieson J. M.
Published: December 2017

Previous experimental studies have revealed that for a given molecular size, the glomerular capillary wall restricts the passage of polyanions more than that of neutral macromolecules, and restricts transport of the latter more than that of polycations. We have developed a theoretical model of this charge-selectivity based on the following principal assumptions: a) all ions (tracer macromolecule and univalent cations and anions) obey a modified Nernst-Planck flux expression, including terms for convection and size-selective retardation; b) the capillary wall has a homogeneous distribution of fixed negative charges; and c) Donnan equilibria exist at the surfaces of this "membrane." To allow specific application of the model we measured electrophoretic mobilities of narrow fractions of dextran sulfate (DS) and diethylaminoethyl dextran (DEAE), and used these to estimate effective molecular charge as a function of molecular size. Based on these measurements and fractional clearance data for DS and DEAE reported previously for the normal Munich-Wistar rat, the capillary wall has an apparent fixed charge concentration of 120--170 meq/liter. The effects of this membrane charge on the filtration of water and on the transcapillary electrical potential difference are also discussed.
Oxygen requirement of bicarbonate-dependent sodium reabsorption in the dog kidney
Authors: Mathisen O. , Monclair T. , Kiil F.
Published: December 2017

The ratio between changes in sodium reabsorption and renal oxygen consumption (Na/O2) was measured in anesthetized dogs at high plasma bicarbonate concentration (32 +/- 1 mM); ethacrynic acid was infused continuously to prevent variations in transcellular NaCl reabsorption when sodium reabsorption was altered by varying plasma PCO2 and glomerular filtration rate (GFR). At high plasma PCO2 (110 mmHg) sodium reabsorption varied in proportion to GRF between 50 and 125% of control GFR (glomerulotubular balance). By reducing PCO2 to 20 mmHg, sodium reabsorption was reduced by 50-60% at constant GFR. The Na/O2 ratio was not significantly different during the two procedures and averaged 48 +/- 2. The ratio between changes in NaHCO3 reabsorption and oxygen consumption averaged 17 +/- 1, which is not significantly different from the Na/O2 ratio of Na-K-ATPase-dependent sodium transport. We propose that NaHCO3 is admitted to the cell by Na+/H+ exchange and that sodium is actively transported by Na-K-ATPase across the peritubular cell membrane; NaHCO3 provides the osmotic force for paracellular reabsorption of water and NaCl (bicarbonate-dependent reabsorption) without additional energy requirement.
Peritubular uptake of lactate by Thamnophis proximal tubule
Authors: Brand P. H. , Stansbury R.
Published: December 2017

Lactate is absorbed in the proximal tubule and also enters tubular cells at the peritubular membrane. To characterize peritubular lactate entry, lactate uptake was measured in isolated nonperfused proximal tubules. Tubules were dissected and incubated in Ringer solution with L(+)-[U-14C]lactate and 3H2O. After incubation, the tubules were extracted, and the extracts were assayed for 14C and 3H or were chromatographed to determine the percentage of tubule 14C identifiable as lactate. Maximal steady-state tubular fluid-to-bath lactate concentration ratios (TF/B lactate) occurred by 30-60 min incubation at 25 degrees C. In 30 min, one-third of the tubules established a TF/B lactate ratio greater than 1.00, and 61.4 +/- 18.6% of tubule 14C was lactate. There was no difference in TF/B lactate ratio in proximal and distal proximal segments. Uptake was depressed at 5 degrees C. Mersalyl at 10(-4) M increased the TF/B lactate ratio and tubule water content. Probenecid at 7.5-30 x 10(-4) M also increased the TF/B lactate ratio. Distal proximal tubules incubated with [3H]PAH showed a control TF/B para-aminohippurate (PAH) ratio of approximately 30, but with 10(-4) M mersalyl the TF/B PAH ratio was approximately 1.00. Lactate uptake at the peritubular membrane occurs against an electrochemical gradient, independently from the PAH transport mechanism.
Inhibition of renin secretion by HCl is related to chloride in both dog and rat
Authors: Kotchen T. A. , Krzyzaniak K. E. , Anderson J. E. , Ernst C. B. , Galla J. H. , Luke R. G.
Published: December 2017

To determine if inhibition of renin release by HCl is related to acidosis or to Cl-, the effects of peripheral venous infusions of HCl and H2SO4 on plasma renin activity (PRA) were compared in the dog and the rat. In NaCl-deprived, pentobarbital-anesthetized dogs, either 0.15 M HCl (n = 10) or 0.075 M H2SO4 (n = 7) was infused for 60 min. In 5 of the 10 HCl-infused dogs (group A), urine Cl- excretion increased (P less than 0.01) during HCl infusion. In the remaining five dogs (group B), Cl- excretion did not increase. Cl- excretion also did not increase during H2SO4 infusion. Comparable acidosis was produced in all three groups. PRA decreased (P less than 0.01) in response to HCl in group A but did not change (P greater than 0.8) in group B HCl-infused dogs or in H2SO4-infused dogs. In NaCl-deprived, anesthetized rats, PRA was suppressed (P less than 0.05) by HCl (from 40.6 +/- 9.4 to 27.4 +/- 5.3 ng . ml-1 . h-1 (SE)) but not H2SO4 (from 37.1 +/- 4.2 to 37.0 +/- 6.3 ng . ml-1 . h-1), despite comparable acidosis. Cl- excretion increased only in HCl-infused rats. In conclusion, inhibition of PRA by acute infusion of HCl is specifically related to Cl-.
How descending limb of Henle's loop permeability affects hypertonic urine formation
Authors: Moore L. C. , Marsh D. J.
Published: December 2017

An isomorphic, dynamic model of the antidiuretic medulla and distal tubule was used to determine how vasa recta (VR) plasma flow and the nature of descending limb (DLH) equilibration influences inner medullary urine concentrating ability in the steady state. Four DLH modes were examined: water recycling with limited solute permeability, ideal water recycling, mixed water-solute recycling, and strict solute recycling. Each DLH mode was evaluated with and without thin ascending limb (tALH) NaCl active transport. Results indicate that VR plasma flow strongly affects medullary solute accumulation, that NaCl reabsorption from passive tALH is insufficient to establish a positive corticomedullary NaCl gradient, that even limited DLH solute entry compromises the medulla's ability to establish an axial osmotic gradient without active transport, and that with tALH active NaCl transport, positive inner medullary NaCl and osmotic gradients could be established with all four DLH modes. We conclude that tALH NaCl active transport or some other form of osmotic work must be invoked to account quantitatively for inner medullary concentrating effects in rodents.
Sulfate transport across the peritubular surface of the marine teleost renal tubule
Authors: Renfro L. J. , Dickman K. G.
Published: December 2017

The uptake of sulfate across the peritubular surface of isolated renal tubules of seawater-acclimated winter flounder, Pseudopleuronectes americanus, consisted of two phases. The fast exchanging component appeared to be a small sulfate compartment with a saturable uptake rate; however, the Km was quite large (14.5 mM). The fast phase was partially inhibited by the anion transport inhibitor 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene (SITS), but was unaffected by antimycin A, which indicated lack of ATP-dependence. The slowly exchanging compartment was fourfold larger than the fast, saturable with a low Km (0.65 mM), and inhibited by antimycin A, SITS, ouabain, and Na-free incubation medium. Phosphate appeared to be a noncompetitive inhibitor of this phase. These observations support the idea that the slow phase of sulfate uptake may be driven by the peritubular membrane Na gradient. This mediated, energy-dependent uptake may be part of the active sulfate secretory pump of the marine teleost renal tubule.
Functional evidence for renorenal reflexes in the rat
Authors: Colindres R. E. , Spielman W. S. , Moss N. G. , Harrington W. W. , Gottschalk C. W.
Published: December 2017

Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.0 +/- 0.6 (SE) vs. 1.9 +/- 0.4%, P < 0.003) occurred in the right innervated kidney in 10 rats. Prior denervation of the right kidney in the other nine rats prevented the renal hemodynamic changes and the fall of urinary volume and of sodium excretion (3.9 +/- 0.6 vs. 4.3 +/- 0.5%) by the right kidney after left renal denervation. Nerve traffic to the right kidney was measured in six other animals after left renal denervation and was found to increase to a mean value 33.8 +/- 6.3% above control levels (P < 0.007) 0-30 min after denervation, with a further significant increase to 66.2 +/- 16.1% above control levels (P < 0.025) 30-60 min after denervation. These results indicate that the functional changes in the right kidney after contralateral renal denervation in volume-expanded rats are caused by a reflex increase in nerve traffic to the right kidney, possibly as a consequence of an interruption of afferent nerve activity originating in the left kidney.
Blood pressure and renal function during chronic changes in sodium intake: role of angiotensin
Authors: Hall J. E. , Guyton A. C. , Smith M. J. , Coleman T. G.
Published: December 2017

The present study was designed to quantitate the role of the renin-angiotensin system (RAS) in determining the chronic relationships between arterial pressure (AP), renal hemodynamics, and Na excretion. In six control dogs, Na balance was achieved during chronic step increases in Na intake from 5 to 500 meq/day with small increases in AP (<7 mmHg), moderate increases in GFR (19%), and decreases in filtration fraction (FF) and plasma renin activity. Similar increases in Na intake in six dogs with angiotensin II (AII) fixed, due to constant intravenous infusion of 5 ng . kg-1 . min-1 AII, caused large increases in AP (42%), GFR (31%) FF, and calculated renal Na reabsorption (TNa) above control. In six dogs with AII formation blocked with SQ 14,225, Na balance at intakes of 5-80 meq/day occurred at reduced AP, GFR, FF, and TNa, although plasma aldosterone concentration (PAC) was not substantially different from that in control dogs. At Na intakes above 240 meq/day, AP was not altered by SQ 14,225. These data indicate that during chronic changes in Na intake the RAS plays a major role, independent of changes in PAC, in allowing Na balance without large changes in GFR or AP. The mechanism whereby AII conserves Na chronically is through increased TNa, since steady-state TNa was increased by AII and decreased by SQ 14,225.
Mechanism of increased potassium secretion in potassium loading and sodium deprivation
Authors: Hayslett John P. , Myketey Nadia , Binder Henry J. , Aronson Peter S.
Published: December 2017

Chronic K loading and Na deficiency increase the capacity of colonic cells to secrete K and are characterized by increases in Na-K-ATPase activity and, as recently shown by our laboratory, the area of basolateral membrane. The present experiments were performed in rat colon to evaluate the quantitative and qualitative changes that occur in the enzyme after induction of K adaptation. Changes in specific binding of [3Hlouabain to a plasma membrane-rich fraction of colonic mucosal cells correlated directly with changes in enzyme activity. In Na-deficient animals the number of ouabain-binding sites increased from 63.6 in controls to 111.2 pmol/mg protein, while the KD for ouabain was unchanged. The Km for ATP was not altered in experimental animals, although Vmax rose twofold. Further studies showed no change in the activity of adenylate cyclase, a marker enzyme for basolateral membrane, in the plasma membrane-rich fraction from experimental cells, although Na-K-ATPase activity increased significantly. These data indicate that increased Na-K-ATPase activity in K-adapted colonic cells reflects an absolute increase in number of pump sites, due, at least in part, to an increase in area of basolateral cell membrane. In addition, in sodium-deprived animals the present data suggest an increase in the density of K pumps in basolateral cell membrane.

Na-K-ATPase; ouabain binding; K adaptation; colonic mucosal cells; kinetics of Na-K-ATPase

Submitted on January 15, 1980

Accepted on April 25, 1980
Luminal Na concentration and the electrical properties of the snake distal tubule
Authors: Beyenbach K. W. , Koeppen B. M. , Dantzler W. H. , Helman S. I.
Published: December 2017

In previous studies of isolated perfused distal tubules of Thamnophis spp., elevation of luminal [Na] from 16 to 150 mM resulted in a transient hyperpolarization of the open-circuit voltage, VToc. To characterize further this response, studies were done to examine the concurrent changes of the transepithelial resistance, RT. After elevation of luminal [Na] from 16 to 150 mM. the VToc increased sharply from a mean of 38.5 to 61.2 mV and the RT decreased from a mean of 22.3 to 15.8 k omega x cm. Thereafter, the VToc declined slowly below control values, and the RT increased well above control values. The short-circuit current calculated as VToc/RT changed in parallel with the VToc, increasing at first (from 1.8 to 4.1 microA/cm) and then falling to about 0.2 microA/cm. Luminal addition of 10(-5) M amiloride caused th VToc leads to 0 and the RT to increase during control and all phases of the transient. On the assumption that RT during amiloride perfusion is the same as the shunt resistance, Rs, the values of the transepithelial driving force, ENa, and its series resistance, RNa, were calculated. An analysis of the data in this way indicated that the principal changes in the epithelium could be attributed to alterations of the RNa and not the ENa or Rs.
Cellular mechanisms of the antiammoniagenic effect of ketone bodies in the dog
Authors: Lemieux G. , Pichette C. , Vinay P. , Gougoux A.
Published: December 2017

To investigate the mechanisms of the antiammoniagenic effect of ketone bodies, acidotic dogs (NH4Cl) were infused with either beta-hydroxybutyrate or acetoacetate. Total blood ketones ranged from 2 to 4 mM. Renal ammoniagenesis fell by a mean of 53%, with a proportional decrease in glutamine extraction. Glutamate release in the renal vein rose, renal extraction of lactate fell, and aspartate and alanine production decreased. Study of the metabolite profile of the renal cortex by the freeze-clamp technique before and after ketone infusion showed that tissue glutamine concentration was unchanged, whereas glutamate, alpha-ketoglutarate, malate, and citrate rose. The intermediates of the gluconeogenic pathway, such as phosphoenolypyruvate, 2-phosphoglycerate, 3-phosphoglycerate, and glucose-6-phosphate, fell significantly. The redox state as calculated from the free NAD+/NADH ratios in the cytosolic (lactate dehydrogenase) and the mitochondrial (glutamate dehydrogenase and beta-hydroxybutyrate dehydrogenase) compartments was reduced. The present study suggests that ketone bodies inhibit renal ammoniagenesis through increased generation of alpha-ketoglutarate (metabolic or bicarbonate effect) and a decrease in the mitochondrial and cytosolic redox potentials in the kidney.
Terminal papillary collecting duct reabsorption of water, sodium, and potassium in Psammomys obesus
Authors: Dobyan D. C. , Arrascue J. F. , Jamison R. L.
Published: December 2017

Micropuncture studies were performed to assess the contribution of the terminal collecting duct to reabsorption of water, sodium, and potassium in the desert rodent, Psammomys obesus. Tubule fluid was collected at base and tip of the exposed papilla before (period I) and after (period II) administration of furosemide. In period I, a significant rise occurred in tubule fluid-to-plasma (TF/P) ratios of inulin, osmolality, and sodium and potassium from base to tip; 2.3 +/- 0.8% of filtered water and 5.1 +/- 1.7% of filtered sodium were reabsorbed by the collecting duct. In period II water, sodium, and potassium delivery to the collecting duct was significantly increased. Although TF/P ratios for inulin, osmolality, and sodium and potassium were lower at base and tip in period II than corresponding values in period I, all ratios increased between base and tip. Approximately 3 times as much water (7.4 +/- 1.8%) and twice as much sodium (10.1 +/- 3.0%) were reabsorbed by the exposed collecting duct in period II. These results reveal a remarkable reabsorptive capacity and suggest that the terminal collecting duct plays an important role in regulation of water and sodium excretion in Psammomys obesus.
Effect of metabolic inhibitors on renal tubule cell volume
Authors: Linshaw M. A.
Published: December 2017

Renal tubule cell volume is thought to be kept constant by a cation pump. Ouabain, by inhibiting Na+-K+-ATPase, blocks cation transport with resultant cell swelling, but the degree of swelling is less than expected were active cation transport completely inhibited. Although the relatively rigid tubule basement membrane may limit swelling of ouabain-treated tubules, some investigators have alternatively postulated that an energy-dependent ouabain-insensitive cation pump regulates cell size. This notion derives from studies of renal cortical slices in which metabolic inhibitors such as 2,4-dinitrophenol (DNP) cause more swelling than ouabain. We blocked cellular metabolism of isolated rabbit proximal straight tubules by adding metabolic inhibitors to or removing acetate and glucose (energy substrate) from the bathing medium and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. In isotonic medium, cell volume increased 36% with addition of 10(-4) M ouabain, 40% with 10(-2) M DNP, 46% with 10(-3) M cyanide, 39% with ouabain + DNP + cyanide, and 37% with removal of bath substrate (P = NS). We conclude that renal tubule cell volume is not regulated by a unique-ouabain-insensitive cation pump.