bluuebunny/crossref_metadata_2025 huggingface dataset:
Separate roles of sodium ion concentration and fluid volumes in salt-loading hypertension in sheep
Authors: Norman RA  , Coleman TG , Wiley TL  , Manning RD  , Guyton AC
Published: December 2017

The goal of these studies was to determine whether the hypertension caused by excessive salt loading results from sodium-induced expansion of the extracellular fluid volume or whether the salt increases the pressure in some other way, such as by causing vascular constriction. In one group of sheep, a combination of total nephrectomy and hemodialysis was used to produce and maintain step increases in extracellular fluid volume for 1 wk without a significant change in sodium ion concentration. In a 2nd group, unilateral nephrectomy, dialysis, and DOCA administration were used to cause step increases in sodium ion concentration while the extracellular fluid volume was held as close to normal as possible. The results showed a 41% increase in arterial pressure in the high-volume sheep and only a 4% increase in pressure in the high-sodium sheep. In both instances the total exchangeable sodium increased almost equally--a 21% increase in the high-sodium sheep. The data support the concept that sodium retention causes hypertension almost entirely because of sodium-induced expansion of the extracellular fluid volume.
Mathematical and mechanical modeling of stress-strain relationship of pericardium
Authors: Rabkin SW , Hsu PH
Published: December 2017

Several mathematical expressions (models) were compared for use in describing the stress-strain (sigma - epsilon) relationship of pericardium. The expression sigma = alpha[ebeta epsilon - 1] was preferred because of its simpler form, theoretical consistency, and "good fit" of experimental data. A method was developed for estimating the precisions of the estimates of the parameters alpha and beta. This approach can have general usefulness in assessing the significance of a change in stress-strain relationship of various soft tissues following different interventions. A mechanical model was formulated for the pericardium which consisted of springs representing the collagen and elastin fibers connected in parallel. It could be simulated by the above equation and could describe the behavior of the pericardium.
Differential labeling with orotic acid and uridine in compensatroy renal hypertrophy
Authors: Ross JS , Malamud D , Caulfield JA , Malt RA
Published: December 2017

Using [5-3H]orotic acid and [5-3H]uridine as precursors, we compared the efficiency of labeling and the localization of labeled RNA during compensatory hypertrophy of the mouse kidney. [5-3H]orotic acid in tubules labeled RNA 15 times more intensely that [5-3H]uridine, presumably because of greater incorporation of orotic acid into tubular cells. Of the orotic acid label, 97% was in tubular cells, mostly in the proximal tubules. Only about 80% of the uridine label was in the tubules; the ratio in proximal tubules compared with that in distal tubules was 2:1. No changes in distribution within the nephron were produced during compensatory hypertrophy. [5-3H]uridine should be used as the precursor of generalized labeling is desired, but [5-3H5orotic acid is the better precursor of RNA for many studies of compensatory hypertrophy since it is more efficient and concentrates in the segments of greatest biologic activity.
Autoregulation of renal blood flow in the puppy
Authors: Jose PA , Slotkoff LM , Montgomery S , Calcagno PL , Eisner G
Published: December 2017

The ability of the immature kidney to autoregulate blood flow was investigated. Renal blood flow was measured by electromagnetic flowmeter. In six puppies, selective blockade of the intrarenal effects of angiotensin II (AII) by [1-sarcosine, 8-alanine]angiotensin II (anti-AII) administered into the renal artery did not change renal blood flow. During selective renal AII blockade, intravenous AII raised perfusion pressure from 76 +/- 2 to 100 +/- 6 mmHg. Renal blood flow increased from 1.59 +/- 0.29 to 1.98 +/- 0.59 ml/g kidney per min, but returned to control levels within 40 s in spite of persistent arterial pressure elevation. In another group of seven puppies, renal blood flow remained constant despite reduction of renal perfusion pressure by aortic constriction to 60 mmHg. In two of these seven puppies intrarenal anti-AII did not abolish autoregulation. Autoregulation of renal blood flow occurs in the puppy and is not influenced by inhibition of angiotensin. The renin-angiotensin system does not appear to be involved in the normal regulation of renal blood flow in the puppy.
Effect of volatile fatty acids on water and ion absorption from the goat colon
Authors: Argenzio RA , Miller N , von Engelhardt W
Published: December 2017

The absorption of volatile fatty acids (VFA) and the influence of VFA on the net transport of inorganic electrolytes and water were examined in the temporarily isolated colon of the conscious goat. Perfusion of the colon with a solution similar in content to that normally present in the cecal outflow showed that the net absorption of VFA was more rapid than that of any other ion present in the solution. When the VFA were replaced with Cl, the net absorption of Na and water was reduced nearly twofold. Increasing the pH of the solution from 6.0 to 7.4 in the presence of VFA also resulted in a twofold decreased in the net transport of Na and water. Perfusion of the colon with a hypertonic solution resulted in approximately zero net water transport; however, the net absorption of Na and VFA continued at similar rates as before. These results support the concept that the colon primarily conserves solute followed by the passive movement of water. They also demonstrate that VFA are rapidly absorbed from the goat colon and indicate a striking influence of VFA on the net transport of Na and water. The presence of VFA in the large intestine may be important for normal absorptive function.
Influence of ammonium ions on mechanical and electrophysiological responses of skeletal muscle
Authors: Heald DE
Published: December 2017

Substitution of ammonium ions for sodium ion initially potentiated and then depressed twitch tension of the frog sartorius muscle. The extent of potentiation and the rate of depression of the twitch were dependent upon the concentration of ammonium ions. Ammonium ion depolarized individual muscle fibers in proportion to concentration. Maximum depolarization (33 mV) occurred in muscles equilibrated in 120 mM ammonium-Ringer for 30 min. At the higher concentration of ammonium (72--120 mM), the potentiation was quickly reversed and the tension response was eliminated completely. The gradual loss of twitch tension was accompanied by progressive decrease in the electrical excitability of individual muscle fibers. Raising the extracellular calcium concentration fivefold reduced the twitch-depressant effect of ammonium ions by maintaining excitability of the muscle fibers. Caffeine contractures (3 and 10 mM) in muscles preequilibrated in 72 mM ammonium-Ringer developed similar tensions to paired controls muscles, but the onset of tension was more rapid in the ammonium-treated muscle. It was concluded that the depression of tension could be accounted for by the loss of membrane excitability and that the evidence did not support the hypothesis that ammonium ions acted at other sites in the excitation contraction coupling.
Vitamin D-dependent, particulate calcium-binding activity and intestinal calcium transport
Authors: Kowarski S , Schachter D
Published: December 2017

A vitamin D-dependent calcium-binding activity of relatively high molecular weight has been identified in the particulate fraction of rat small intestinal mucosa. The Ca-binding activity is sedimented at 140,000 X g after treatment of the mucosal particulate fraction with Triton X-114. Intestinal brush-border suspensions can also be used as starting material. The Ca-binding component is inactivated by heat and repeated freeze-thawing and consists of one or more protein complexes in the range of 0.5-1.0 million mol wt as indicated by gel filtration. The Ca-binding activity correlates positively with known features of the intestinal Ca transport mechanism, as demonstrated by studies of the distribution in the small intestine and the effects of vitamin D, dietary Ca, cycloheximide treatment, and rat age. It is suggested that the component might function in the transit of Ca across the brush-border surface to the cytosol of intestinal mucosal cells.
Arterial pressure-flow relations in the awake standing dog
Authors: Enrlich W , Schrijen FV , Solomon TA , Rodriguez-Lopez E , Riley RL
Published: December 2017

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.
Effects of autonomic neurohumors on transmembrane potentials of atrial plateau fibers
Authors: Davis LD
Published: December 2017

Isolated canine atrial plateau fibers were treated with acetylcholine or norepinephrine to note the effects on the transmembrane potential. Acetylcholine, 1.0 or 2.0 mug/ml, consistently reduced the slope of inherent phase 4 depolarization. Increases in maximum diastolic potential and rising velocity occurred along with a decrease in overshoot. The plateau phase disappeared. Pretreatment with atropine, 1.0 mug/ml, prevented these responses, and alone this drug had no discernible effect. Norepinephrine consistently increased the slope of phase 4 depolarization. Frequently plateau fibers generated action potentials by the normal pacemaker mechanism. "Arrhythmias" characterized by spontaneous excitations were induced in 92% of the norepinephrine experiments. Norepinephrine also enhanced the plateau phase of the action potential and decreased the rising velocity and overshoot. Racemic propranolol, 1.0 mug/ml, blocked all the above effects including arrhythmias. Dextropropranolol, 1.0 mug/ml, did not block effects produced by norepinephrine. Acetylcholine, applied to fibers under treatment with norepinephrine, reduced the slope of norepinephrine-induced phase 4 depolarization and terminated induced arrhythmias.
Effects of carotid hypotension on aortic hemodynamics in the unanesthetized dog
Authors: Cox RH , Fronek A , Peterson LH
Published: December 2017

The effects of occlusion of the brachiocephalic artery on aortic hemodynamics were assessed in 12 chronically instrumented dogs in the unanesthetized state. Continuous measurements of ascending aorta pressure and flow were made. In the steady state following occlusion, heart rate increased by 36% and mean arterial pressure by 45%, while cardiac output was unchanged from preocclusion levels. Hydraulic power delivery to the systemic circulation by the left ventricle was increased during occlusion, while the fraction of total power associated with pulsations decreased. Values of peripheral resistance and ascending aorta input impedance were both increased during occlusion. Graded occlusions of the brachiocephalic artery produced graded, monotonic increases in the entire aortic impedance spectrum between 2 and 20 Hz with more sensitive responses occurring with the smaller, submaximal responses. Considered with results of previous studies, these results suggest that activation of smooth muscle in large conduit arteries is also associated with the pressor response which accompanies carotid hypotension and that such activation has a hemodynamically significant effect.
Permeability of the rabbit colon in vitro
Authors: Yorio T. , Bentley P. J.
Published: December 2017

The rabbit colon, in vitro as everted-sac or diaphragm preparations, exhibits a transmural PD, as high as 70 mV, a short-circuit current (SCC) of 100 to 150 muA cm-3 and a resistance of 300–500 omega-cm2. It maintains these functions for at least 3 h. The SCC can be abolished by amiloride or increased by amphotericin B. Na, Cl, and K flux measurements showed a net influx (mucosa to serosa) of Na and a net efflux of K. The SCC can be accounted for by the movements of these ions. The SCC in the presence of amphotericin B was nearly equivalent to the net Na flux. Amiloride abolished the net Na transfer but did not ht (Ktrnas X 10(7)) for water was 5,000 cm s-1 while that for urea was 26 cm s-1. The rabbit provides a viable pn and the present observations appear to be consistent with its physiological role.
Effect of secretin on renal blood flow, interstitial pressure, and sodium excretion
Authors: Marchand G. R. , Ott C. E. , Lang F. C. , Greger R. F. , Knox F. G.
Published: December 2017

Most renal vasodilators are natriuretic. However, secretin increases renal blood flow (RBF) markedly but produces only a very slight increase in sodium excretion (UNaV). To investigate this observation further, the relationship between vasodilatation, interstitial pressure (IP), and UNaV was studied in dogs. Intrarenal infusion of secretin increased RBF (delta=107+/-19 ml/min). The IP, as measured from chronically implanted polyethylene matrix capsules, was not significantly changed (delta=-0.3+/-0.5 mmHg). UNaV was slightly, although significantly, increased (delta=19+/-4 mueq/min). Following a similar increase in RBF with an intrarenal infusion of acetylcholine (ACh), IP and UNaV increased markedly (delta=8.2+/-0.8 mmHg and 174+/-23 mueq/min, respectively). Neither secretin nor ACh) altered glomerular filtration rate or blood pressure. Both secretin and ACh produced comparable increases in peritubule capillary(delta=5+/-1 and 7.5+/-1.4 mmHg, respectively) and free-flow tubule pressure (delta=7+/-2 and 9.5+/-1.4 mmHg, respectively). In summary, the usual relationship between vasodilatation and IP was dissociated during secretin infusion, whereas the relationship between IP and natriuresis was not dissociated.
Bicarbonate ions in active sodium transport across toad bladder
Authors: Chen J. S. , Walser M.
Published: December 2017

The conductance, ga, and electromotive force, E, of active ion transport across toad bladders mounted as sacs were estimated from electrical measurements made before and after addition of sufficient ouabain (1.89 X 10(-3) M) to eliminate spontaneous potential. The ratio of net sodium transport (estimated from bidirectional fluxes) to external current in bladders voltage clamped to 0 mV was significantly less than unity in a normal medium containing HCO3- and Cl- ions, and also when Cl- was replaced with SO42-. However, when acetazolamide was added or when HCO3- was replaced by phosphate, short-circuit current and net sodium transport became equal. Spontaneous potential, E, and ga were all reduced about 20% by these maneuvers. The response of bidirectional sodium fluxes to voltage clamping at 0 mV or 120 mV in a bicarbonate-free medium was otherwise similar to that observed in a normal medium: net flux varied linearly with potential and calculated fluxes in the active transport path indicated a value significantly greater than unity for the empirical constant Q in the equation for change in the flux ratio, f, with change in potential, psi, viz., delta ln f = Q(ZF/RT)delta psi, similar to the high value for this constant that we have found in a bicarbonate-containing medium. We conclude that bicarbonate ions facilitate active sodium transport and also may be actively transported from serosa to mucosa in Dominican toads. However, coupling between bicarbonate and sodium fluxes does not account for the high value for Q for sodium in the active transport path.
Stimulation of renin release in perfused kidney by low calcium and high magnesium
Authors: Fray J. S.
Published: December 2017

These experiments were designed to test whether changing perfusate calcium or magnesium concentrations affected renin release in the isolated perfused rat kidney, and whether kidneys removed from sodium-loaded or sodium-deprived rats released the same amount of renin in response to identical stimuli. Kidneys were perfused with Kreb-Henseleit solution containing albumin. Renin release was inversely related to perfusate calcium concentration, whereas renin release was directly related to perfusate magnesium. Although a low calcium medium or low perfusion pressure (50 mmHg) stimulated renin release, the release was substantially greater in the sodium-deprived rats. Increasing the perfusate sodium concentration from 85 to 206 mM increased excretion, but did not alter renin release. It is concluded that a) low perfusate calcium and high magnesium concentrations stimulate renin release, b) kidneys removed from sodium-deprived rats released substantially more renin thatn those from sodium-loaded rats, and c) changing perfusate sodium concentration alters sodium excretion, but does not affect renin release.
Prostaglandins and the kidney
Authors: Dunn Michael J. , Hood Virginia L.
Published: December 2017

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cycle-oxygenase in the kidney to PGE2, PGF2α, PGD2, and, possibly, to PGI2, and thromboxane A2. Production of PGE2, and PGF2α, is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2α and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.

prostaglandin synthesis; renin-angiotensin; hypertension; antidiuretic hormone
Tubular localization of adaptation to dietary phosphate in rats
Authors: Muhlbauer R. C. , Bonjour J. P. , Fleisch H.
Published: December 2017

The renal tubule of rats adapts its transport capacity for inorganic phosphate (Pi) in response to changes in dietary Pi intake. Tubular localization of this adaptation was studied in rats pair-fed for 10 days a low (LPD), i.e., 0.2 g/100 g, or a high (HPD), i.e., 1.8 g/100 g, phosphorus diet. Free-flow micropunctures under acute Pi infusion were made at elevated but similar filtered loads of Pi: LPD, 6.07 +/- 0.29 (n, 32); HPD 5.34 +/- 0.24 (n, 33) micromol/kidney per min. Fractional excretion of Pi (FEPi) for the whole kidney was: LPD, 0.26 +/- 0.02 (n, 32); HPD, 0.67 +/- 0.02 (n, 33) (P less than 0.001). The fraction of filtered Pi found at various puncture sites suggests that part of the adaptation to dietary Pi occurs in the early proximal tubule. An effect in the later portion of the proximal convoluted tubule cannot be excluded in the present experiments. Furthermore, dietary Pi affects markedly the difference in Pi delivery between distal tubule and final urine. This could be due to a greater adaptive response of deep nephrons. Alternatively, the results could also indicate that an adaptation with a secretory component takes place along the terminal part of the nephrons.
Comparative study on development of corticosterone and DOCA hypertension in rats
Authors: Haack D. , Mohring J. , Mohring B. , Petri M. , Hackenthal E.
Published: December 2017

The administration of corticosterone for 5 consecutive days to normal rats on a standard sodium intake induced negative sodium and water balance. These effects were opposite those observed under DOCA treatment. However, not only under DOCA but also under corticosterone treatment extracellular fluid volume (ECFV) and plasma volume (PV) increased, and blood pressure (BP) rose in parallel. Plasma renin and angiotensin II concentrations declined under the influence of both steroids. Plasma arginine vasopressin concentrations increased under DOCA, whereas they transiently decreased under corticosterone administration. These data suggest that the common mediator for BP elevation due to steroid excess would be an increase in ECFV and PV. The pathways by which this increase is achieved seem to be different. Under DOCA treatment ECFV and PV increased subsequent to renal sodium and water retention. Under corticosterone, however, sodium and water were shifted from intra- to extracellular compartments, and a fraction of this shifted sodium and water was conserved in extracellular space, most likely because corticosterone also affected renal sodium handling.
Transport of H+ against electrochemical gradients in turtle urinary bladder
Authors: Al-awqati Q. , Mueller A. , Steinmetz P. R.
Published: December 2017

Active H+ transport (JH) by the isolated turtle bladder was inhibited by either an applied chemical gradient (deltapH) or an electrical gradient (deltapsi). The relation of JH to either deltapH or deltapsi was linear, and the slopes and the force gradients required to bring JH to zero were similar with both methods. The transport system was analyzed in terms of an equivalent circuit model comprising a proton motive force (PMF), an active conductance (LH) in series with the pump, and a parallel or passive conductance which may be ignored in this preparation. Increasing ambient PCO2 markedly increased JH and the active conductance (as deltaJH/deltadeltapH) but had no effect on the apparent PMF (PMF'). Similarly, acetazolamide caused comparable decreases in JH and LH without change in PMF'. Inhibition of metabolism by deoxygenation, deoxy-D-glucose, or depletion of metabolic substrate caused large decreases in JH and LH with reduction in PMF' of less than 14%. Glucose addition increased JH and LH but caused a slight decrease in PMF'. Thus, the experimental maneuvers affected the transport rate primarily through changes in the active conductance. Since PMF' was little affected, the force of the pump must be determined by factors other than the metabolic driving reaction alone. Conductance factors relating to transport as well as to metabolism participate in controlling PMF.
Maturation of diluting capacity in loop of Henle of rat superficial nephrons
Authors: Zink H. , Horster M.
Published: December 2017

The postnatal development of renal diluting capacity was studied by free-flow micropuncture and by microdissection of single superficial loops of Henle in rats kept on a high salt diet. Total renal filtration rate, sodium absorption, total solute excretion, and systemic arterial pressure were monitored during single nephron evaluation at two maturational stages (12–15 days and 27–35 days postnatal). Nephron filtration rates were identical when measured in early distal and late proximal segments of the same nephron. Absolute fluid absorption between these sites increased by a factor of 2.5, whereas loop fractional absorption of the volume load changed from 38.1 +/- 6.9 to 49.8 +/- 4.8% (SD), while proximal volume delivery to the loop increased from 4.33 +/- 1.12 to 7.14 +/- 0.65 nl/min. Simultaneously, the osmolarity of early distal fluid (8.8% of distal length) decreased significantly from 284 + 19.8 to 180.9 +/- 18.2 mosmol/liter during maturation. This study suggests that the ability of the loop of Henle to generate hypotonic fluid is attained only gradually during ontogeny. Volume absorption in the loop of Henle increases disproportionately to the loop volume load.
Site of formation of kinins in the dog nephron
Authors: Scicli A. G. , Gandolfi R. , Carretero O. A.
Published: December 2017

The site of formation of kinins in the nephron was determined by stop-flow studies in dogs. Klinin, inulin, sodium, potassium concentrations were measured in the fractions collected during the stop-flow procedures. In addition, in three of the 17 stop-flow experiments, kallikrein activity was also measured. The highest kinin concentration after correction for water reabsorption was found in the fractions that were probably trapped in the distal part of the nephron. Either one or two peak was located either in the fraction overlapping (in one instance) or in the fractions coming prior to the fractions with the highest concentration of potassium. This first peak was present in all but one of the stop-flow experiments and was greater than the second peak. The second peak of kinins was found in 13 of the 17 stop-flow exeriments and was located in the fractions with the lowest sodium concentration. Those fractions with the lowest sodium concentration. Those fractions with the lowest sodium concentration also had the highest kallikrein concentration. No evidence of kinin formation was found in the fractions representing the proximal nephron. We conclude, therefore, that kinins are formed in the distal part of the nephron, with the highest concentration found in the last part of the distal nephron and/or in the renal papilla and pelvis.
Effects of constituent amino acids on tubular handling of microinfused angiotensin II
Authors: Pullman T. N. , Carone F. A. , Oparil S. , Nakamura S.
Published: December 2017

[14C]angiotensin II ([14C]AII) was microinjected alone or with excess L-isoleucine (IIe) or L-aspartic acid (Asp) into renal tubules of anesthetized rats. Urinary excretion of 14C-labeled material was measured, and the intact peptide and its metabolites were identified and quantified. When isoleucine was administered with [14C]AII, urinary recovery of the 14C-labeled material increased directly with distance of infusion site from glomerulus, and most of the radioactivity in urine was [14C]Ile. The data suggest that isoleucine interfered with reabsorption of [14C]Ile derived from hydrolysis of [14C]AII and less so with the hydrolysis itself. When aspartic acid was administered with [14C]AII into the proximal 5/6 of the proximal convolution, total urinary recovery of the 14C-labeled material was unchanged, but percentage of recovery as [14C]AII increased; with infusion into the distal 1/6 of the proximal convolution, total urinary recovery of the 14C labele increased. The data suggest that aspartic acid interfered with the enzymatic hydrolysis of [14C]AII and reabsorption of isoleucine. In distal tubules the 14C label was almost completely recovered as intact [14C]AII in all protocols. The results show that free amino acids influence proximal tubular handling of small linear peptides in rats.
Quantitation of renal uric acid synthesis in the chicken
Authors: Chin Theodore Y. , Quebbemann A. J.
Published: December 2017

The contribution of uric acid synthesized in the kidney (nephrogenic uric acid) to the total uric acid excreted in the urine was studied in the chicken by use of the isotope-dilution technique. In the nonfasted chicken the urine-to-plasma specific activity ratio (SAR) of [14C]uric acid was 0.83, suggesting that a minimum of 17% of the uric acid excreted in the urine is synthesized in the kidney. During allopurinol infusion into the renal portal circulation of one kidney the SAR increased to 0.99, indicating that the renal synthesis of uric acid was almost completely inhibited and that the SAR is a valid indicator of the contribution of nephrogenic uric acid excreted into the urine without first entering the circulation. Chickens fasted for 18 h showed a lower rate of renal synthesis of uric acid. Hypoxanthine infusion into the systemic circulation increased the rate of renal synthesis of uric acid in both fasted and nonfasted chickens, suggesting that circulating precursor levels may in part regulate the renal synthesis of uric acid.

kidney; specific activity ratio; allopurinol; renal metabolism

Submitted on July 14, 1977
Calcium transport across peritubular surface of the marine teleost renal tubule
Authors: Renfro J. L.
Published: December 2017

Isolated renal tubules of seawater-acclimated flounder (Pseudopleuronectes americanus) readily accumulated Ca and Mg when exposed to increased concentrations of these ions. Evidence based on the ability of the tubules to maintain high K levels indicated that the Ca was neither free in the cytosol nor taken up by mitochondria. Two phases of Ca uptake were seen. The fast phase was kinetically complex and not affected by Mg, dinitrophenol, cytochalasin B, or Na-free medium, but was stimulated by ouabain. The slow phase showed Michaelis-Menten kinetics and was inhibited by Mg and dinitrophenol, but was stimulated by Na-free medium, cytochalasin B, and ouabain. The slow phase was also more responsive to changes in bath Ca activity and was thought to be involved with the powerful divalent cation secretory system of these tubules. No correlation between divalent cation uptake and fluid content of the tubules was seen.
Calcium in the control of renin release
Authors: Park C. S. , Malvin R. L.
Published: December 2017

The effect of Ca concentrations in the incubation medium and of estimated intracellular Ca concentrations on renin release was examined with use of pig renal cortical slices. In addition, the Ca requirement for the epinephrine stimulatory effect and for the ouabain inhibitory action on renin release was also tested. In mediums containing 5.9 mM K, variations in Ca concentration had no effect on renin release. In contrast, when the K concentration was 59 mM, a significant inhibition of renin release was attained with all concentrations of calcium. The inhibition of renin release in high K mediums by Ca was attributed to an increase in the intracellular Ca concentration. In addition, both the stimulatory effect of epinephrine and the inhibitory effect of ouabain on renin release required Ca in the medium. These results support the hypothesis that the control of renin secretion is mediated, in part, by changes in the intracellular concentration of Ca, most likely in the juxtaglomerular cells.
The control of sodium excretion
Authors: de Wardener H. E.
Published: December 2017

The kidneys of a normal man filter approximately 24,000 meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq change in 24-h urinary sodium excretion. The control of urinary sodium excretion, therefore, depends, first, on ensuring that the bulk of the sodium is reabsorbed, a function which is carried out in the proximal tubule and ascending loop of Henle. Second, it depends on adjusting the reabsorption of the small quantity of sodium which is delivered into the collecting duct so that the amount excreted in the urine is that required to maintain sodium balance. The bulk reabsorptive mechanisms can be considered as buffers to prevent large fluctuations in the amount of sodium delivered to the collecting duct, thus facilitating the fine adjustments of reabsorption which are made at this site. In conditions other than extreme salt loading or deprivation, changes in sodium reabsorption in the proximal tubule and loop of Henle probably have little, if any, effect on urinary sodium excretion. Sodium reabsorption in the proximal tubule and the collecting duct appears to be influenced by unidentified circulating substances.
Ion selectivity and proximal salt reabsorption
Authors: Berry C. A. , Warnock D. G. , Rector F. C.
Published: December 2017

Electrophysiological techniques were used in isolated perfused superficial (S) and juxtamedullary (JM) rabbit proximal convoluted tubules (PCT) to examine the relative sodium-to-chloride (PNa/PCl) and bicarbonate-to-chloride (PHCO3/PCl) permeability ratios. We found that the great majority of PCT are sodium selective and that PHCO3/PCl depends on the experimental conditions. In the presence of active sodium transport, PHCO3/PCl is high and increases with PNa/PCl. When PHCO3/PCl is determined after inhibition of active sodium transport or at 25 degrees C, PHCO3/PCl approximates the free solution anion mobility ratio of 0.5 and is independent of PNa/PCl. The difference between PHCO3/PCl determined in the presence of and in the absence of active transport suggests that the lowering of bath bicarbonate concentration in the presence of active transport changes both paracellular and transcellular current flow. In addition, we found that during luminal perfusion with high chloride, low bicarbonate, organic solute-free solutions, the transepithelial electrical potential depends on PNa/PCl and PHCO3/PCl. This potential is approximately 4.0 mV in S PCT with low PNa/PCl and falls progressively to zero in JM PCT with high PNa/PCl. From these data we conclude that anion concentration gradients drive an important diffusive flux of sodium chloride through the paracellular pathway only in PCT with low PNa/PCl ratios.
Separate renal function studies in conscious dogs with renovascular hypertension
Authors: DeForrest J. M. , Davis J. O. , Freeman R. H. , Watkins B. E. , Stephens G. A.
Published: December 2017

A new method was developed for separate kidney function studies by catheterizing the ureters and exteriorizing the catheters through the urethra into the vagina. Renal artery plication was performed to reduce blood flow to one kidney by 66 +/- 5%. Arterial pressure increased from 107 +/- 2 to 131 +/- 3 mmHg and remained elevated for 28 days. Plasma renin activity was increased for the first 7-10 days only. Sodium and water excretion were markedly reduced in the kidney with the stenosed renal artery and after the first 2 days Na and water excretion were incresed in the contralateral kidney. These changes in Na and water excretion were frequently associated with similar directional changes in glomerular filtration rate (GFR) and renal plasma flow. An exception was noted in that renal sodium and water excretion remained low throughout the 28 days in the kidney with the constricted renal artery, whereas GRF returned to near the control level by the end of 2 wk. Altered filtration fraction did not appear to be a determining factor in control of the rate of Na excretion. It is suggested that GFR, the renin-angiotensin-aldosterone system, and other as yet undefined factors are involved in salt and water homeostasis during unilateral renal artery stenosis with hypertension.
Calcium and sodium transport by the distal convoluted tubule of the rat
Authors: Costanzo L. S. , Windhager E. E.
Published: December 2017

Calcium and sodium transport were studied in the distal convoluted tubule of the rat by micropuncture and microperfusion techniques. The animals received either control infusions, 0.9% saline at 0.02 ml/min, or chlorothiazide (CTZ), 0.5 mg/min-kg. In free-flow micropuncture, distal calcium reabsorption occurred against an electrochemical gradient; it was 9% of the filtered load in the controls and 13.8% in the CTZ-treated rats. The drug dissociated calcium and sodium transport along the distal tubule. Absolute reabsorptive rates for calcium and sodium, measured in pump perfusion experiments, were proportional to the distal loads. CTZ, acting from the lumen, enhanced net calcium (P less than 0.01) and reduced net sodium (P less than 0.01) reabsorption. In stationary microperfusion experiments, sodium backflux produced rapid establishment of a steady-state concentration of 50 mM. In contrast, net backflux of calcium was negligible. With calcium in the luminal perfusion fluid, there was a concentration-dependent reabsorptive efflux which was not saturated at a luminal calcium concentration of 9.5 mM and which was enhanced by CTZ.
Carbonic anhydrase-dependent bicarbonate reabsorption in the rat proximal tubule
Authors: Lucci M. S. , Warnock D. G. , Rector F. C.
Published: December 2017

The extent to which bicarbonate reabsorption in the rat proximal convoluted tubule depends on carbonic anhydrase has been examined by in vivo microperfusion and the measurement of total CO2 concentration by microcalorimetry. Tubules were perfused with an ultrafiltrate-like solution at 13 nl/min, and volume reabsorptive rate (JV) was measured using [14C]inulin. Addition of either 800 or 100 microM acetazolamide to the perfusion solution completely inhibited the reabsorption of total CO2. The control total CO2 reabsorptive rate (JtCO2) was 147 +/- 23 pmol/mm.min, and acetazolamide reduced JtCO2 to -3 +/- 5 pmol/mm.min. Acetazolamide reduced JV by 65% from a control of 2.3 +/- 0.4 to 0.8 +/- 0.1 nl/mm.min. The dose-response curve for acetazolamide showed that the I50 for inhibition of JtCO2 was 4 microM. The inactive congener of acetazolamide, t-butyl acetazolamide, did not reduce JV or inhibit bicarbonate reabsorption, indicating that the effect of acetazolamide on JtCO2 was specific for carbonic anhydrase inhibition. Since bicarbonate reabsorption was completely blocked by carbonic anhydrase inhibition, there is no need to postulate either carbonic acid recycling or carbonic anhydrase-independent bicarbonate reabsorption.
Regulation of cell volume in separated renal tubules incubated in hypotonic medium
Authors: Paillard M. , Leviel F. , Gardin J. P.
Published: December 2017

The regulation of cell volume was studied in separated renal tubules (SRT) whose basement membrane had been removed by collagenase. Regulation occurred when SRT were immersed in a hypotonic medium, the increase in cellular water content being half that expected in the absence of regulation. Regulation was immediate, with no initial swelling, and was accompanied by a loss of NaCl, with no change in cellular K. This regulation was eliminated by 10(-3) M ouabain. We conclude that: 1) Cell volume regulation which occurs in a hypotonic medium is due to an immediate loss of NaCl. 2) Loss of NaCl might be due to blocking of the net passive NaCl entry into the cells resulting from the drop in the transmembrane NaCl electrochemical gradient. The high membrane sodium permeability, probably located on the luminal side of the tubular cells, might explain why regulation was instantaneous. 3) Elimination of volume regulation by ouabain suggests there is no need to assume that a ouabain-insensitive pump regulates cell volume.
Renal and nephron hemodynamics in spontaneously hypertensive rats
Authors: Arendshorst W. J. , Beierwaltes W. H.
Published: December 2017

Renal and nephron hemodynamics were compared between anesthetized, nondiuretic, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although the mean arterial pressure was higher in SHR than in WKY, 158 VS. 114 mmHg, glomerular filtration rate (GFR) and renal blood flow (RBF) were similar in both groups. So were intrarenal hydrostatic pressures, single nephron GFR (SNGFR), and single nephron blood flow (SNBF). Accordingly, the increased renal vascular resistance (RVR) in SHR was due to predominant preglomerular vasoconstriction. In a second group of SHR, SHR-AC, the femoral arterial pressure was reduced acutely to 114 mmHg by means of aortic constriction above the renal arteries. The mean values for GFR, RBF, SNGFR, SNBF, and intrarenal hydrostatic pressures resembled those in SHR, whereas RVR was less in SHR-AC. These autoregulatory adjustments of RVR were again largely limited to the preglomerular vasculature. Efferent arteriolar resistance was similar in all three groups. We conclude that the enhanced RVR in 12-wk-old SHR is primarily a consequence of a physiological, autoregulatory response of afferent arteriolar resistance to the elevated arterial pressure. Further, RVR in SHR is not fixed and constant but responds appropriately to reductions in renal perfusion pressure.
Luminal Na+ entry into Necturus proximal tubule cells
Authors: Kimura G. , Spring K. R.
Published: December 2017

The dependence of intracellular Na+ activity on the electrical driving force across the luminal membrane and the presence of Cl- in the luminal perfusate was studied in Necturus proximal tubule. Intracellular Na+ and K+ activities were measured with microelectrodes filled with liquid ion exchanger. Perfusion of the tubule lumen with a NaCl-free solution caused cell Na+ activity to fall from the control value of 29.7 to 6.6 mM. In the absence of luminal driving force across the luminal membrane in accordance with simple diffusion of Na+ across this membrane. When the tubule lumen contained Na+ and Cl-, an electrically neutral component of Na+ entry into cells from the lumen appeared in addition to the diffusional component of Na+ entry.
Voltage dependence of calcium transport in the thick ascending limb of Henle's loop
Authors: Bourdeau J. E. , Burg M. B.
Published: December 2017

Thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen-to-bath and bath-to-lumen were measured with 45Ca using different solutions that caused the transepithelial voltage to vary over a wide range. With lumen-positive voltages there was net calcium absorption from lumen to bath which varied directly with the voltage. With voltage near zero there was no measurable net flux. When the voltage was made negative, the direction of net calcium transport reversed (i.e., secretion from bath to lumen). The presence or absence of bicarbonate in the lumen did not affect the calcium fluxes. Calcium permeability, calculated from the dependence of net flux on voltage, was 7.7 x 10(-6) cm/s, which is approximately 25% of the sodium permeability previously determined in this segment. Analysis of the calcium flux ratios revealed interdependence of the bidirectional fluxes consistent with single-file diffusion but no evidence for active calcium transport. We conclude that there is an important component of passive net calcium transport driven by the voltage in this segment.
Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism?
Authors: Cohen J. J.
Published: December 2017

It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a "low" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.
Renin inactivation during in vitro experiments
Authors: Cho K. W. , Malvin R. L.
Published: December 2017

Experiments were designed to clarify the factors affecting renin released during in vitro experiments. Kidneys from rat, dog, and pig were used. Experiments were done in which the gas phase was either bubbled through the incubation medium or layered above it. Renin released into the incubation medium disappeared very rapidly when gas was bubbled through the medium. The decline was similar in mediums bubbled with oxygen-CO2 (95%--5%) or nitrogen-CO2 (95%--5%). The half-life of renin activity in the bubbled medium was approximately 15 min in both cases. However, in experiments in which nonbubbled medium was used throughout, renin released into the incubation medium did not disappear after removal of slices. These data are interpreted to mean that the renin released into the incubation medium is inactivated at the air-water interface.
Intrarenal renin and autoregulation of renal plasma flow and glomerular filtration rate
Authors: Murray R. D. , Malvin R. L.
Published: December 2017

Autoregulatory responses of renal plasma flow (RPF) and glomerular filtration rate (GFR) to reductions in renal artery pressure (RAP) were studied in both kidneys of two-kidney, one-clamp dogs and in dogs treated with deoxycorticosterone acetate (DOCA; 25 mg/kg) plus high sodium diets with and without renal arterial clamping. In non-DOCA-treated animals, unilateral renal artery constriction resulted in a significant difference (P = 0.004) in renal renin activity (RRA) between the clamped (171 +/- 37 ng AI.mg-1.h-1) and the contralateral (57 +/- 23 mg AI.mg-1.h-1) kidneys with no change in their relative autoregulatory ability. In dogs treated with DOCA/high sodium there were no differences in RRA between the clamped and contralateral kidneys. The dogs treated with DOCA/high sodium were able to autoregulate both RPF and GFR even though their RRA was only 5.4 ng AI.mg-1.h-1. DOCA/high sodium treatment, however, reduced basal RPF (22%) and GFR (23%) below those in non-DOCA-treated animals. Analysis of the autoregulatory ability of individual kidneys showed no relationship to either RRA or renin secretory rates. These results support the conclusion that the renin-angiotensin system is not necessary component in the autoregulation of RPF or GFR.