bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal cyclic AMP accumulation and adenulate cyclase stimulation by erythropoietic agents
Authors: Rodgers GM , Fisher JW , George WJ
Published: December 2017

The regional distribution of cyclic AMP in the kidney was determined following erythropoietic stimulation with hypoxia and cobalt. Following these stimuli, increases in renal cyclic AMP concentrations were restricted to the cortex. The basis for this localization in the case of cobalt treatment was found to reside in the stimulation of renal cortical adenylate cyclase activity in vitro by concentrations of cobalt similar to those found in vivo. The level of cobalt in the cortex after cobalt treatment was found to approach 500 mumol/kg of tissue, whereas no detectable levels of cobalt were found in the renal medulla. Additionally, other agents such as parathyroid hormone and lactic acid, that are known to lack stimulatory effects on medullary adenylate cyclase, were found to stimulate the cortical enzyme. This stimulation of renal cortical adenylate cyclase correlates with enhanced erythropoiesis as demonstrated by increased radiolabeled iron incorporation into erythrocytes. These results support previous reports which suggest that renal cortical cyclic AMP mediates erythropoietin production in response to erythropoietically active agents.
Potassium transport in the distal tubule and collecting duct of the rat
Authors: Reineck HJ , Osgood RW , Ferris TF , Stein JH
Published: December 2017

Because of recent conflicting results, micropuncture studies were performed to clarify the respective role of the distal convoluted tubule and collecting duct in the regulation of urinary potassium excretion. Five groups of Sprague-Dawley rats were studied: group I, hydropenia (n = 10); group II, Ringer loading (n = 7); group III, acute KC1 loading (n = 6); group IV, mannitol diuresis (n = 6); group V, KC1 infusion during mannitol diuresis (n = 7). Early and late distal tubules were identified with intravenous injections of lissamine green. In each animal net secretion of potassium occurred along the distal convoluted tubule, and a direct relationship between distal tubular flow rate and potassium secretion was observed. The magnitude of potassium secretion at high distal tubular flow rates was dependent on the model studied. Potassium transport beyond the distal tubule was evaluated by comparing end distal potassium delivery and fractional potassium excretion. At low urinary flow rates net reabsorption was observed, whereas at higher flow rates no net transport occurred. Thus, flow rate along the collecting duct may be a major determinant of urinary potassium excretion.
Factors determining superficial nephron filtration in the mature, growing rat
Authors: Tucker B. J. , Blantz R. C.
Published: December 2017

Factors that determine and cause an increased glomerular filtration rate in superficial nephrons (sngfr) in the mature, growing rat were examined in 39 Munich-Wistar rats, ranging from 93 to 335 g in body weight, from 40 to 140 days in age, and in sngfr, from 15 to 78 nl/min. Hydrostatic pressure gradient (delta P) from glomerular capillary (PG) to Bowman's space (Pt) was measured in surface glomeruli and pertinent oncotic pressures (pi) by microprotein methods. Isoncotic plasma expansion (PV) prevented filtration-pressure equilibrium (EFP) and permitted calculation of glomerular permeability coefficient (LpA) where sngfr = EFP-LpA, and EFP = delta P - pi. Increased sngfr correlated best with nephron plasma flow (rpf) (r = 0.81, P less than 0.001) and LpA (r = 0.71, P less than 0.001). The rpf increased because of parallel reductions in afferent and efferent resistances (slope = 0.89 +/- 0.09, r = 0.86, P less than 0.001), which also produced a constancy of PG and deltaP with growth. The ratio of rpf to LpA remained constant with growth permitting EFP to remain relatively unchanged (r = 0.14, P greater than 0.4). The increase in LpA should permit filtration-pressure equilibrium to persist in the hydropenic rat in spite of increases in rpf with growth. deltaP was constant with increasing age and therefore did not contribute to the increase in sngfr.
A micropuncture study of salt and water retention in chronic experimental cirrhosis
Authors: Lopez-Novoa J. M. , Rengel M. A. , Rodicio J. L. , Hernando L.
Published: December 2017

The object of this study was to localize increased sodium resorption in rats with chronic hepatic cirrhosis. Cirrhosis was induced by the administration of phenobarbital and carbon tetrachloride. The animals retained salt and water after loading and showed edema and ascites. Salt and water balance, clearance, and micropuncture tests were performed. Five or six weeks after the start of procedures to induce injury, the rats were unable to excrete salt and water loads promptly. Urine flow and sodium concentration were significantly less in cirrhotic rats with edema and ascites than in the normal controls. The glomerular filtration rate was slightly lower in the right, nonmicropunctured kidney but was the same in the left. The nephron glomerular filtration rates of surface nephrons were equal in both the experimental and control rats. The fractional proximal resorption rate was notably greater in cirrhotic rats, as was the total proximal nephron resorption rate. That increased proximal resorption alone might account for diminished sodium and water excretion cannot be demonstrated from this study, although we believe that major evidence is provided of the importance of proximal resorption in this phenomenon.
Influence of prostaglandins on sodium transport of isolated medullary nephron segments
Authors: Fine L. G. , Trizna W.
Published: December 2017

The possibility that prostaglandins (PG) located in the renal medulla may influence renal excretion of sodium by a direct tubular action was examined by the addition of prostaglandins PGE2, PGF2alpha, and PGA2 to the peritubular and luminal surfaces of isolated perfused medullary thick ascending lumbs and collecting tubules from rabbit kidneys. The prostaglandins at both high (2.5 x 10(-4) M) and low (10 (-10) M, 10 (-7) M) concentrations had no effect on transepithelial potential difference and net sodium flux across these segments. Pretreatment of the animals with indomethacin did not influence the results. In vivo, both PGE2 and PGF2alpha, caused a natriuresis when infused directly into one renal artery, whereas PGA2 had no effect on sodium excretion. The prostaglandin inhibitors indomethacin, meclofenamate, and RO 20-5720 similarly had no direct effect on sodium transport in the nephron segments studied. It is concluded that the previously observed influence of prostaglandins and prostaglandin inhibitors on renal excretion of sodium in vivo are not mediated by a direct tubular action.
Effect of parathyroid hormone on urinary acidification
Authors: Arruda J. A. , Nascimento L. , Westenfelder C. , Kurtzman N. A.
Published: December 2017

The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption.
Dependence of the driving force of the sodium pump on rate of transport
Authors: Feig Peter U. , Wetzel Gayle D. , Frazier Howard S.
Published: December 2017

The driving force for active transport of Na+ in the isolated toad bladder, ENa, was measured as the reciprocal slope of the change in conductance with change in short-circuit current after stimulation with antidiuretic hormone. The base-line short-circuit current was altered by change in ambient Na+ concentration or addition of amiloride, maneuvers which alter availability of Na+ at the site of active transport. In the absence of a chemical gradient for Na+ across the bladder, ENa was found to be inversely related to the rate of Na+ transport, a finding incompatible with the simple electrical analogue that has been proposed for the system. The results provide additional support for the view that ENa measured in this way has both energetic and kinetic components.

membrane transport; active transport; sodium transport; ENa

Submitted on April 23, 1976
An analysis of the determinants of nephron filtration rate
Authors: Tucker B. J. , Blantz R. C.
Published: December 2017

Studies on glomerular filtration in the Munich-Wistar rat, a strain with surface glomeruli, have permitted for the first time the evaluation of the four factors that determine filtration rate: 1) the rate of nephron plasma flow (RPF), 2) the glomerular hydrostatic pressure gradient (deltaP) from capillary to Bowman's space, 3) systemic oncotic pressure (piA), and 4) the glomerular permeability coefficient (LpA), and their respective roles in producing change in filtration rate. The process of filtration in the Munich-Wistar rat is characterized by filtration pressure equilibrium and, therefore, filtration should be highly plasma flow-dependent. Analysis of data from this strain suggests that multiple factors can change LpA, and, at least in animals which do not achieve filtration pressure equilibrium, these alterations in LpA can influence the final filtration rate. Multivariate statistical analysis in a variety of experimental conditions in the Munich-Wistar rat suggest that changes in RPF remain the major mediator of change in nephron filtration rate, both in rats at filtration pressure equilibrium and in disequilibrated animals. Although the glomerulus is an ultrafilter driven by hydrostatic forces, changes in deltaP assume a lesser role in producing alterations in filtration rate.
Response of phosphate transport to parathyroid hormone in segments of rabbit nephron
Authors: Dennis V. W. , Bello-Reuss E. , Robinson R. R.
Published: December 2017

The effects of bovine parathyroid hormone (PTH) on phosphate transport were examined in proximal convoluted tubules, proximal straight tubules, and cortical collecting ducts isolated from the rabbit kidney. The lumen-to-bath flux of phosphate (JlbPO4) and the bath-to-lumen flux (JblPO4) were measured simultaneously with [33P]phosphate and [32P]phosphate. In the proximal convoluted segments perfused with an ultrafiltrate of normal serum, PTH reduced the fluid absorption rate from 1.21 +/- 0.10 to 0.60 nl/mm-min but did not affect JlbPO4, which averaged 5.45 +/- 0.97 pmol/mm-min, or JblPO4, which was 0.50 +/- 0.08 pmol/mm-min. During perfusion with low bicarbonate-high chloride fluids at pH 7.4, the PTH-induced changes in fluid absorption were eliminated but no change occurred in phosphate transport. On the other hand in proximal straight segments JlbP04 was lower at 2.64 +/- 0.41 pmol/mm-min and was directly inhibited by PTH to 1.90 +/- 0.34 pmol/mm-min (P less than 0.001). Net phosphate transport was not observed in cortical collecting ducts in the presence or absence of PTH. These data suggest that phosphate absorption in the proximal tubule involves more than one transport system, that the effects of PTH on fluid absorption are not interdependent with the effects on phosphate transport, and that the proximal straight tubule appears to be an important site of PTH-sensitive phosphate transport.
Na-K-activated ATPase: activity maturation in rabbit nephron segments dissected in vitro
Authors: Schmidt U. , Horster M.
Published: December 2017

Single, defined nephron segments were dissected in vitro from fresh slices of neonatal and mature rabbit kidney. Na-K-ATPase was quantified for six different tubule segments with an ultramicromethod. The enzyme distribution pattern in the neonatal nephron was similar to that in the mature nephron. Activity in distal segments was 2-5 times higher than proximal tubule activity referred to tissue dry weight, and 2 times higher referred to tubule length. Neonatal enzyme activity was lower than mature in all segments. Some segments carried only 23% of mature activity. Enzyme activity in the proximal convoluted tubule was constant during maturation when referred to the basal and lateral membrane area measured in the same developmental stages. In vitro activities of these tubules were similar to the enzyme activity measured previously in freeze-dried slices. The Vmax during development of Na-K-ATPase was higher by a factor of 5 in the mature tubule, whereas the Km was identical in the neonatal and mature tubule. The ouabain-insensitive ATPase did not show a maturational activity change.
Renal excretion of phosphate and calcium in parathyroidectomized starlings
Authors: Clark N. B. , Wideman R. F.
Published: December 2017

Renal excretion patterns of calcium, phosphate, sodium, and potassium were studied in parathyroidectomized (PTX) and parathyroid extract (PTE)-injected PTX starlings. Sturnus vulgaris. Anesthetized birds (Equi-Thesin or Dial) were infused intravenously with 2.5% mannitol containing [14C]inulin. PTX caused significant hypocalcemia, hyperphosphatemia, increased relative calcium clearance (CCa/CIn), and decreased relative clearances of phosphate and potassium, but did not change the clearance of sodium. Glomerular filtration rate (GFR=CIn) and urine flow remained unchanged up to 2 h after PTX. PTE administration 3 h after PTX returned serum calcium and phosphate values to control levels and caused a transient (10-min) increase in GFR. Following PTE, the relative clearances of phosphate, sodium- and potassium increased, while that of calcium decreased significantly relative to the PTX levels. PTE caused net tubular secretion of phosphate, decreased tubular reabsorption of sodium and potassium (sometimes potassium secretion), and a return of excretion of calcium to control levels. These studies indicate that the parathyroid role in calcium and phosphate homeostasis in starlings is predominantly on the kidney.
Ontogeny of glycine transport in isolated rat renal tubules
Authors: Roth K. S. , Hwang S. M. , London J. W. , Segal S.
Published: December 2017

Isolated renal tubule preparations were made from newborn Sprague-Dawley rats and used to study initial entry rate kinetics of glycine. The results were compared to those obtained in the isolated tubule preparation from the adult rat kidney. While initial rates of glycine uptake were identical for newborn and adult tubules, significant differences in influx kinetics were demonstrated. Of the two apparent transport Km systems shown to be present in the newborn tubule, the high-affinity, low-capacity system accounts for about 40% of total glycine uptake at physiologic concentrations. The high-affinity, low-capacity system of the adult tissue accounts for about 10% of total uptake at the same concentration range. The data lend strength to the argument against the concept that the physiologic hyperglycinuria of the newborn rat is due to either impaired ability to concentrate glycine intracellularly or to absence of one or more transport mechanisms for glycine.
Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique
Authors: Williams R. H. , Thomas C. , Bell D. , Navar L. G.
Published: December 2017

Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.
Renal hemodynamics in the rat before and during inhibition of angiotensin II
Authors: Arendshorst W. J. , Finn W. F.
Published: December 2017

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.
Mechanism of active chloride transport by urinary bladder of the Colombian toad
Authors: Soboslai G. B. , McTigue M. , Weiner M. W.
Published: December 2017

In order to investigate the mechanism of active chloride transport, experiments were performed to verify the previous report that removal of potassium from the solutions bathing the urinary bladders of Colombian toads induced a reversal of short-circuit current (RSCC) and active chloride transport. The present experiments confirmed these findings. However, there was no correlation between the magnitude of the RSCC and the chloride transport. Furthermore, removal of chloride from the mucosal bathing solutions did not markedly affect the RSCC, indicating that the chloride transport was electrically silent. Removal of bicarbonate from the bathing solutions eliminated the RSCC, and acetazolamide inhibited both the RSCC and net chloride transport. These findings suggest a relationship between chloride and hydrogen ion transport. Inhibition of sodium transport by removal of sodium or addition of ouabain or amiloride has previously been shown to produce an RSCC. In the present experiments these same maneuvers caused an RSCC and induced net chloride transport. It is concluded that active chloride transport by Colombian toad bladder is stimulated by inhibition of sodium transport. The inhibition of active chloride transport by acetazolamide suggests a possible role for carbonic anhydrase in this process.
Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine
Authors: Ito H. , Coe F. L.
Published: December 2017

Urine contains nondialyzable inhibitors of calcium oxalate crystal growth. We have pursued the hypothesis that these inhibitors may, in part, be acidic peptides and polyribonucleotide fragments. Homopolyribonucleotides and RNA inhibit calcium oxalate crystal growth at 5 x 10(-6) M of constituent ribonucleotide, whereas the monomer nucleotides are inactive at 10(-4) M. Poly-L-aspartic or glutamic acid are also inhibitory at 5 X 10(-6) M of amino acid, whereas the monomeric amino acids are inert. Gastric pepsin, a naturally occurring acidic peptide, is inhibitory. Incubation with nonspecific protease reduced the inhibitory effectiveness of normal human urine consistently and significantly, a fact compatible with an important contribution of peptides. A variable additional reduction was produced by subsequent treatment with ribonuclease, suggesting only a small role for polyribonucleotide. Sequential ion exchange and gel filtration chromatography and preparative disc gel electrophoresis yielded inhibitory material enriched with peptides that were strongly acidic and high in proline. Peptides and ribonucleotides seem to contribute to urinary nondialyzable crystal growth inhibitory activity.
Localization of central sites of action of angiotensin II on ADH release in vitro
Authors: Gregg C. M. , Malvin R. L.
Published: December 2017

It is now thought that angiotensin II can stimulate antidiuretic hormone (ADH) release in vivo by a direct action in the central nervous system but it is not known whether the locus of stimulation is the hypothalamus or the neurohypophysis or both. Isolated rat neural lobes incubated for 10 min in buffer containing angiotensin II (200 ng/ml or 2 microgram/ml) did not increase ADH release compared to control values, but addition of KCl (60 mM) to the bath markedly stimulated ADH release. However, intact hypothalamoneurohypophysial systems (containing the supraoptic nuclei) incubated with angiotensin II (200 ng/ml or 2 microgram/ml) did show a pronounced stimulation of ADH release. The data support the hypothesis that angiotensin II, at least in vitro, has a central effect on ADH release which is at the level of the hypothalamus.
Characteristics of glucose-phlorizin interactions in isolated proximal tubules
Authors: Brazy P. C. , Dennis V. W.
Published: December 2017

Characteristics of phlorizin's interaction with the bidirectional fluxes of glucose were examined using isolated proximal convoluted tubules from the rabbit kidney. Radioisotopic glucose fluxes were determined with artificial perfusates having glucose concentrations of 5-15 mM. Rabbit serum was used as the bath. Phlorizin in intraluminal concentrations of 10(-7) to 10(-4) M progressively reduced the lumen-to-bath flux of glucose without affecting the bath-to-lumen flux. At 10(-4) M phlorizin in the lumen, the lumen-to-bath flux decreased from 92.86 +/- 5.71 to 7.83 +/- 3.04 pmol/mm.min (P less than 0.001), with bath-to-lumen fluxes averaging 4.58 +/- 0.58 pmol/mm-min. Similar changes occurred when phlorizin was added to the bath, although concentrations approximately 10-100 times higher were required. Phlorizin 10(-3) M in the bath also reduced the bath-to-lumen glucose flux from 10.20 +/- 3.07 to 7.16 +/- 2.20 pmol/mm.min (P less than 0.05). Phlorizin transport was passive. The kinetics of phlorizin's inhibition of the lumen-to-bath glucose flux were determined by varying the glucose delivery rate over a range of phlorizin concentrations. Phlorizin reduced the maximal glucose transport rate and increased the delivery rate of glucose at which glucose absorption was half maximal. These data indicate that the interaction of phlorizin with proximal renal glucose transport involves elements of both competitive and noncompetitive inhibition.
Nephron heterogeneity of phosphate reabsorption
Authors: Haas J. A. , Berndt T. , Knox F. G.
Published: December 2017

Previous micropuncture studies in rats have demonstrated that fractional phosphate delivery (FDP%) from superficial distal nephrons is higher than in urine. To determine whether this apparent reabsorption could be accounted for by a lower FDP% from the deep nephrons, FDP% was determined in free-low micropuncture from deep nephrons (DN) (ascending limb of the loop of Henle in the papilla), superficial nephrons (SN) (distal tubules in the cortex), and urine (duct of Bellini). In six acute thyroparathyroidectomized (TPTX) rats, FDP% in DN was significantly less than SN. The urinary fractional phosphate excretion (FEP%) was significantly less than in the SN, but not significantly different from the DN. In six chronic TPTX rats, FDP% in DN was significantly less than in SN. The urinary FEP% was significantly less than the FDP% in the SN, and significantly less than the FDP% in the DN, evidence which favors phosphate reabsorption in the terminal nephron. We conclude that in TPTX rats, which are conserving phosphate, deep nephrons reabsorb phosphate more avidly than superficial nephrons.
Phenomenological model relating cell shape to water reabsorption in proximal nephron
Authors: Welling D. J. , Welling L. W. , Hill J. J.
Published: December 2017

If the complex pattern of intercellular channels in proximal tubule is determined in part by the forces of large transepithelial water flow, the shape of the cells is an indicator of the type and magnitude of the forces required for water movement and the routes of that flow. To test this thesis, morphologic data and volume flow parameters for rabbit proximal tubule are related generally by a mass balance equation. If the intercellular boundaries are assumed to be highly deformable and to respond to changes in hydrostatic pressure, the solution to that equation is a simple relationship between cell shape and the forces required for water movement. The resulting phenomenological model suggests an important new role for peritubular serum proteins and can be used to compute reasonable values for cell wall hydraulic conductivity, intercellular protein diffusion constant, and a channel fluid osmolality not more than 1% greater than that of luminal fluid. It is concluded that quantitative morphologic studies may serve as a powerful means for evaluating and understanding transport phenomena in the nephron.
Muscle buffer values
Authors: Larsen L. A. , Burnell J. M.
Published: December 2017

The in vitro skeletal and cardiac muscle buffer values have been determined for normal and potassium-depleted dogs. Depletion produced a statistically significant decrease in buffer value for both skeletal 66 vs. 61 sl, and cardiac muscle, 64 vs. 55 sl. The decreased cardiac muscle buffer value was obtained despite no statistically significant loss of cardiac muscle potassium.
Thermistor use to monitor urine flow rates in dogs
Authors: Hyde R. J. , Lohse C. L. , Testoni F. J.
Published: December 2017

The small size of a new thermistor flowmeter facilitated implantation in ureters in anesthetized dogs. It consisted of a self-heating thermistor bead which was suspended centrally within an open catheter and dissipated heat as a function of fluid velocity. A continuous record of instantaneous flow rate was obtained, since the flowmeter catheter maintained a constant cross-sectional area around the thermistor bead. A continuous record of volume output was obtained simultaneously with an additional measurement technique. Spurt volumes of urine delivered in concert with ureter peristalsis were directly correlated to peak flow rates delineated by the flowmeter.
Changes in the plasma anion gap during chronic metabolic acid-base disturbances
Authors: Adrogue H. J. , Brensilver J. , Madias N. E.
Published: December 2017

A basic premise in the utilization of the plasma anion gap in the assessment of acid-base disorders is that this parameter remains constant during hyperchloremic metabolic acidosis and metabolic alkalosis. Experimental data under in vitro conditions, however, cast serious doubt on this premise. The purpose of the present study was to characterize the plasma anion gap, estimated as (Na + K) - Cl + HCO3), in two large groups of dogs with graded degrees of chronic, HCl-induced metabolic acidosis or chronic, diuretic-induced metabolic alkalosis. The data indicate that the plasma anion gap decreases significantly in HCl acidosis and increases significantly in metabolic alkalosis; the predicted mean anion gap in animals with a plasma bicarbonate concentration of 10, 21 (normal), and 40 meq/liter approximated 13, 18, and 26 meq/liter, respectively. The observed variation in the plasma anion gap is interpreted as originating mainly from directional changes in the net negative charge of plasma proteins; these changes result from the titration process secondary to the altered plasma acidity and, in the case of metabolic alkalosis, from the additional effect of an increased plasma protein concentration.
Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis
Authors: Oster J. R. , Perez G. O. , Vaamonde C. A.
Published: December 2017

Metabolic acidosis is known to be associated with increased blood potassium and phosphorus concentrations but the influence of mineral versus nonmineral acids on these variables remains undefined. Therefore, we infused anesthetized mongrel dogs with 0.45% saline (controls), the mineral acids HCl and NH4Cl, and the nonmineral acids lactic, beta-hydroxybutyric and methyl malonic for 1-3 h. Administration of both mineral acids was associated with significant increases in plasma potassium. In contrast, infusion of the three monmineral acids did not result in increases in plasma potassium; in fact, the levels decreased initially in the majority of the dogs. Phosphorus concentrations were increased by lactic and beta-hydroxybutric acids, were unchanged by NH4Cl and HCl, and were decreased by methyl malonic acid. Although the mechanisms responsible for these changes remain to be elucidated, the findings indicate that short-duration infusion of mineral and nonmineral acids has substantially different effects on plasma concentrations of these predominantly intracellular ions.
Blunted norepinephrine natriuresis in the isolated spontaneously hypertensive rat kidney
Authors: Steele T. H. , Underwood J. L.
Published: December 2017

In order to characterize the relationship between blood pressure and renal sodium handling in the Kyoto spontaneously hypertensive rat (SHR), we did renal clearance and isolated perfusion studies in SHR and Wistar-Kyoto controls (WKY). Clearance studies revealed no differences in renal function between SHR and WKY. Isolated perfused kidneys from SHR demonstrated a diminished glomerular filtration rate (GFR) compared to WKY kidneys when both were perfused at normotensive pressures. Increasing the perfusion pressures to hypertensive levels by adjusting the perfusate flow rate increased both the GFR and sodium excretion to equivalent values. However, the addition of norepinephrine 15 ng/ml, to the perfusate resulted in a far greater natriuretic response in WKY kidneys than in SHR, despite equivalent increases in perfusion pressures, renal resistances, GFR, and filtration fractions. These results suggest that norepinephrine exerts a direct or indirect inhibitory action on renal sodium transport, and this effect is diminished in SHR kidneys. Additionally, abnormalities in renal sodium transport may play a role in the pathogenesis of hypertension in the SHR.
Effect of natural variations in PaCO2 on plasma [HCO3-] in dogs: a redefinition of normal
Authors: Madias N. E. , Adrogue H. J. , Cohen J. J. , Schwartz W. B.
Published: December 2017

Graded degrees of both chronic hyper- and hypocapnia are known to induce renal responses that significantly alter plasma bicarbonate concentration. These findings have raised the possibility that even normal variations in PaCO2 play an important role in determining the exact level of bicarbonate in plasma. To test this hypothesis, we examined the relationship between resting levels of PaCO2 and the plasma bicarbonate concentration in two groups of normal dogs, one ingesting a normal salt diet and the other a salt-restricted diet. The results indicate that values for bicarbonate within the normal range are highly dependent on the prevaling level of carbon dioxide tension ([HCO3-] = 0.35 PaCO2 + 9.0, r = 0.72). Accordingly, approximately 50% of the normal variance in bicarbonate concentration is explained simply by the variance in PaCO2. The joint confidence region for bicarbonate concentration and PaCO2, which can be derived from these data, provides a new and more rigorous definition of the normal range for acid-base values in the dog.
Renal handling of calcium: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3
Authors: Hugi K. , Bonjour J. P. , Fleisch H.
Published: December 2017

The influence of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the renal Ca handling was studied in vitamin D-replete rats. The relation between plasma concentration ([Ca]P) and urinary Ca (UCaV/ml GF) was ascertained by clearance techniques over the [Ca]P range of 1.4-3.4 mM varied by infusion of Ca gluconate. Chronic thyroparathyroidectomy (TPTX) decreased the plasma Ca threshold from about 2.3 to 1.5 mM. Between [Ca]P 1.4 and 3.4 mM there was a linear increase in UCaV/ml GF corresponding to 35-50% of the increment in filtered load. In TPTX, PTH (2.5 IU/h i.v.) shifted the Ca threshold from 1.5 to 2.3 mM, without changing the slope of UCaV/ml GF on [Ca]P. The effect of TPTX on the renal Ca handling was not corrected by doses of 1,25(OH)2D3, which increased the intestinal Ca absorption of TPTX rats to normal level. In intact and TPTX rats disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given at doses which inhibit the production of 1,25(OH)2D3 did not change the tubular Ca handling. Furthermore, 1,25(OH)2D3 had no effect in EHDP-treated TPTX rats. Therefore, tubular Ca handling does not appear to be altered in response to chronic endogenous variation or physiologic supplementation of 1,25(OH)2D3 in vitamin D-replete rats. This is in contrast to the marked alteration observed after TPTX or PTH administration.
Local intrarenal vasoconstrictor-vasodilator interactions in mild partial ureteral obstruction
Authors: Ichikawa I. , Brenner B. M.
Published: December 2017

Page F131: I. Ichikawa and B. M. Brenner. “Local intrarenal vasoconstrictor-vasodilator interactions in mild partial ureteral obstruction.” In Tables 1 and 2 (page F135) and Table 5 (page F138) the overbar for mean femoral arterial pressure, AP, and for mean glomerular transcapillary hydraulic pressure difference, ΔP, was inadvertently lost in the printing process. Tables 1 and 2: column 3 heading should be AP, mmHg; column 6 heading should be ΔP, mmHg; column 11 heading should be ∏E/P. Table 5: column 11 heading should be ∏E/ΔP.
Calcium transport in the nephron
Authors: Suki W. N.
Published: December 2017

Ionized and complexed calcium are filtered at the glomerulus and more than 95% of the filtered load is reabsorbed along the length of the nephron. In the proximal convoluted tubule calcium is absorbed in proportion to sodium and water, suggesting a passive mechanism. The high permeability of this segment is compatible with passive transport, but evidence for active transport has been advanced. A role for Ca2+-ATPase and/or for a Ca2+/Na+ antiport has also been proposed. The straight portion of the proximal tubule appears to transport calcium actively but little is known about the mechanism and regulation of calcium absorption in this segment. Both passive and active transport of calcium in the thick ascending limb have been demonstrated, and heterogeneity in the function of medullary and cortical segments has been proposed. Definite evidence has been advanced for avid active calcium absorption in the distal convoluted tubule. Both chlorothiazide and parathyroid hormone enhance the transport of calcium in this segment. The granular portion of the collecting tubule resembles in its properties and function the distal convoluted tubule. The light portion, however, is incapable of transporting calcium. The distal tubule and collecting tubule may be the final regulators of urinary excretion of calcium but much more data are required before this view can be adopted.
Renal tubular reabsorption in spontaneously hypertensive rats
Authors: Arendshorst W. J. , Beierwaltes W. H.
Published: December 2017

We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 ml.100 g body wt-1.h-1) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.
Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats
Authors: Moore L. C. , Schnermann J. , Yarimizu S.
Published: December 2017

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.
Nonpressor mechanisms in CNS-induced natriuresis
Authors: Mouw David R. , Vander Arthur J. , Bourgoignie Jacques J. , Kutschinski Sandra S. , Mathias Nancy P.
Published: December 2017

Ventriculocisternal perfusion was performed in pentobarbital-anesthetized dogs. Perfusion of high Na (300 mM NaCl) artificial cerebrospinal fluid (CSF) (E) for 2 h was preceded by 2 h of control (C) and was followed by 2 h of recovery (R) during which normal (150 mM NaCl) artificial CSF was perfused. A time-control group was perfused with normal artificial CSF throughout C, E, and R. High sodium perfusion resulted in a marked natriuresis in each of nine animals and suppression of plasma renin activity. There were no simultaneous changes in mean arterial pressure, glomerular filtration rate, or renal plasma flow. Sodium excretion and plasma renin activity showed a slight gradual rise in the time-control group, but no significant differences were observed between the C and E periods; sodium excretion and plasma renin activity were similar in the high Na and time-control groups during C and R, but significantly different during E. It is concluded that when CSF sodium is elevated by perfusing artificial CSF, the resulting natriuresis and suppression of plasma renin activity are not caused by hemodynamic changes.

antidiuretic hormone; natriuretic hormone; renin; renal hemodynamics; cerebrospinal fluid; osmoreceptors; sodium receptors

Submitted on July 17, 1978

Accepted on April 10, 1979
Optical techniques for the evaluation of epithelial transport processes
Authors: Spring K. R.
Published: December 2017

Light microscopic observation of living epithelial tissues is a powerful analytical tool in the investigation of solute and water transport. New techniques in quantitative microscopy permit the determination of epithelial cell size and shape as well as accurate measurements of lateral intercellular space dimensions. Traditional techniques for the study of epithelial cell function may be used in conjunction with continuous quantitation of tissue morphology. Fluorescent probes of membrane, cell, and interspace function may be monitored at low light levels to obtain information about the dynamic behavior of the preparation. Application of some of these methods to the Necturus gallbladder epithelium has enabled determination of lateral cell membrane compliance, the hydrostatic pressure equivalent to active transport, the intracellular NaCl transport pool, the rate of active NaCl transport, and the flux of NaCl into the cell across the apical membrane. Possible future applications of optical techniques include measurement of water permeability, solute reflection coefficients, fluid flow paterns, and interspace osmolality.
Effect of potassium deficiency on papillary plasma flow in the rat
Authors: Whinnery M. A. , Kunau R. T.
Published: December 2017

Chronic potassium (K+) deficiency has been shown previously to cause a reduction in solute content in the renal papilla, an effect that is potentially important as a contributing factor to the concentrating defect seen in this circumstance. The cause of the decrease in papillary solute content has not been adequately explained. Because alterations in the blood flow rate through the renal papilla may affect the solute content of the papilla, the present experiments examined the effect of chronic K+ deficiency on papillary plasma flow (PPF) in the rat. PPF was measured by the radioactive albumin accumulation technique. Sprague-Dawley rats were fed identical quantities of water and either a normal or a K+-deficient diet for 21 days. Total GRR in the control rats, 1.7 +/- 0.17 (SE) ml/min, was similar to that in K+-deficient rats, 1.4 +/- 0.14 ml/min (P greater than 0.01). Total [3H]PAH clearance was also comparable in the two groups, i.e., 4.4 +/- 0.47 in control and 4.7 +/- 0.45 ml/min in K+-deficient rats (P greater than 0.06). PPF was significantly lower in K+-deficient rats, 19.7 +/- 1.1 ml-min-1-100 g-1, than in control rats, 59.8 +/- 1.6 ml-min-1-100 g-1 (P less than 0.001). The decrease in PPF in the K+-deficient rat may reflect a reduction in perfusion to the juxtamedullary nephrons, thereby resulting in a diminution in both solute delivery and blood flow to the papilla.
Anatomy of the juxtaglomerular apparatus
Authors: Barajas L.
Published: December 2017

The juxtaglomerular apparatus, located in the glomerular hilum, consists of a vascular component (afferent and efferent arterioles and extraglomerular mesangium) and a tubular component (macula densa). Two types of contact between vascular and tubular components are observed: a) a complex type, involving distal tubule, extraglomerular mesangium, and proximal efferent arteriole, and b) a simple type, consisting of apposition of the basement membranes of the vascular and tubular components. Juxtaglomerular granular cells, the source of renin, are present throughout the vascular component but are more numerous in the afferent arteriole. They can be considered as "myoendocrine" cells, since they contain myofibrils and attachment bodies, together with secretory granules and crystalline protogranules. Macula densa cells differ from those elsewhere in the distal tubule in that their nuclei are closer to each other, the Golgi apparatus is basally located, and their basal membrane infoldings are less prominent. Adrenergic nerves are demonstrable by fluorescence histochemistry in the juxtaglomerular region. Electron microscopy reveals unmyelinated nerve fibers containing small dense-cored vesicles and capable, as shown by ultrastructural autoradiography, of incorporating exogenous tritiated norepinephrine. Neuroeffector junctions occur between nerves and cells of the vascular and, less frequently, the tubular component. In addition, adrenergic axons are observed in a juxtaglomerular cell tumor. Nerve terminals are seen in direct contact with the tumor cells.
Chronic blockade of angiotensin II formation during sodium deprivation
Authors: Hall J. E. , Guyton A. C. , Smith M. J. , Coleman T. G.
Published: December 2017

The present study was designed to investigate the mechanisms by which the renin-angiotensin system (RAS) regulates arterial pressure (AP) and renal function during chronic sodium deprivation. Intravenous infusion of the converting enzyme inhibitor SQ 14225 (14 microgram.kg-1.mm-1) for 8 days in 12 sodium-deficient dogs caused a marked decrease in AP from 90 +/- 1 to 67 +/- 2 mmHg and a reduction in glomerular filtration rate (GFR), filtration fraction (FF), and plasma aldosterone concentration (PAC). Despite the fall in AP and GFR, urinary Na excretion and effective renal plasma flow (ERPF) increased above control levels. In four dogs, infusion of aldosterone (200 micrograms/day) for 8 days during continuous SQ 14225 infusion restored PAC to levels above control, but did not significantly change AP or renal function from the values observed during SQ 14225 infusion alone. However, infusion of angiotensin II (AII) (10 or 20 ng.kg-1.min-1) for 5––8 days during continuous SQ 14225 infusion almost completely restored AP and renal function to control levels. These data indicate that the RAS plays a major role in regulating AP, renal hemodynamics, and Na excretion during Na deprivation, probably through the direct effects of AII rather than through changes in PAC.
Influence of mucosal and serosal pH on antidiuretic action in frog urinary bladder
Authors: Parisi M. , Chevalier J. , Bourguet J.
Published: December 2017

Mucosal acidification to pH 6.5 reduced by 88% the oxytocin- (2.2 x 10(-8) M) elicited increase of water permeability in frog urinary bladder. Mucosal alkalinization (pH 10.5) increased by as much as 200% the response to the same concentration of oxytocin. These effects were not observed when supramaximal concentrations of oxytocin were imployed. Similar changes were found when the serosal pH was modified. The hydrosmotic responses elicited by serosal hypertonicity or cyclic AMP plus theophylline were also affected by mucosal or serosal changes of the hydrogen in concentration, suggesting an effect at a post-cyclic AMP level. Important interactions were found between luminal pH and serosal hypertonicity when experimental conditions were employed similar to those observed in the collecting duct of mammalian nephron. Freeze-fracture studies showed that the number of intramembranous aggregates of particles induced by ADH in the luminal membrane was reduced by mucosal acidification and augmented by an increase in medium pH.