Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney

Summary Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10^–6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C _In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

The effect of antidiuretic hormone on the distribution of nephron filtration rates in rats with hereditary diabetes insipidus

Summary The effect of antidiuretic hormone on the distribution of nephron filtration rates was studied in rats with hereditary diabetes insipidus using the Hanssen method for determination of nephron filtration rates as modified by de Rouffignacet al. [18]. Conversion of water diuresis to antidiuresis by infusion of ADH resulted in a moderate, but highly significant increase in the filtration rate of the juxtamedullary nephrons, while the nephrons of all other cortex regions filtered at an unaltered rate. A mechanism based on the action of ADH on distal nephron water permeability is proposed as an explanation: water inflow into the medulla very likely decreases when water diuresis is converted to antidiuresis. This occasions a rise in medullary osmolality which then causes an increase in the apparent viscosity of the blood flowing through the vasa recta. This is responsible for a rise in juxtamedullary postglomerular resistance which results in an increase in the effective filtration pressure and thus in the juxtamedullary nephron filtration rate. The results suggest that an increased juxtamedullary filtration rate participates in the establishment and maintenance of the inner medullary solute gradients, possibly as a consequence of an increased solute delivery to the ascending limbs of the long loops of Henle.This work was supported by the Deutsche Forschungsgemeinschaft.On leave from the University of Melbourne as a recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

The tubulo-glomerular feedback mechanism — a determinant for the autoregulation of the glomerular filtration rate in superficial and juxtamedullary nephrons

Summary The intrinsic myogenic hypothesis and the tubuloglomerular feedback mechanism (TGF) give the presently most cherished explanation to the autoregulation of renal blood flow and glomerular filtration rate. A series of experiments was performed on young, normohydrated rats in order to evaluate the importance of TGF as an autoregulatory factor of the single nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephron populations. Micropuncture techniques were applied to tubular structures of the renal surface and on the papilla for the measurement of hydrostatic pressures and SNGFR. The SNGFR was also measured with a modified Hanssen technique. A TV-technique was used to record the urine free flow rate in the loop of Henle.The net driving forces for glomerular filtration at the afferent end of the glomerular capillaries were estimated to be 19 and 47 mm Hg for superficial and juxtamedullary nephrons respectively, when the urine flow at the macula densa was zero. The SNGFR of the two nephron populations amounted to 29.6 and 84.1 nl·min^–1·g^–1 K.W., as measured with the micropuncture technique. With a modified Hanssen technique the corresponding values were 25.8 and 27.7 nl·min^–1. g^–1 K.W. (kidney weight).The SNGFR was found to be well autoregulated when the urine flow at the macula densa was intact, but not when the urine flow was interrupted.The flow rate in the loop of Henle was in free flow conditions 7.3 nl·min^–1·g^–1 K.W. which shall be compared with 19.2 nl·min^–1·g^–1 K.W. when the urine flow to the macula densa was zero.We conclude that SNGFR is mainly autoregulated by the TGF-mechanism in young, normohydrated rats at lower arterial pressures. In normal conditions TGF is highly activated for juxtamedullary nephrons, but not for the superficial ones. The high urine flow rate in the loop of Henle at reduced flow rates at the macula densa may invalidate the use of loop blockade in studies of water and solute transfer across the loop walls.     

Evidence for tubuloglomerular feedback in juxtamedullary nephrons of young rats

To determine whether the filtration rate of juxtamedullary nephrons is regulated by tubuloglomerular feedback (TGF), we developed two micropuncture techniques suitable for the papilla of young rats. One consisted of measuring the tubular flow in descending limbs of Henle loops (VDLH) while the ascending limbs of the loop of Henle (ALH) were perfused at various rates with three different solutions: modified Ringer, artificial Henle loop solution, and Ringer containing 10(-4) M furosemide. SNGFR was also measured in several juxtamedullary nephrons. The other protocol consisted of measuring the tubular stop-flow pressure (PSF) in descending limbs of the loop of Henle upstream to a wax block. Distal to the block Ringer was perfused at various rates through ALH. Our results provide the first evidence of a TGF response in juxtamedullary nephrons. VDLH and SNGFR decreased during Ringer perfusion to 42 +/- 4 and 44 +/- 4% of their values at zero perfusion. The same pattern was observed using Henle loop solution as perfusate, whereas with furosemide VDLH did not change. The maximal decrease in PSF was 14.1 +/- 1.4 mmHg. The perfusion rate necessary to induce a half-maximal PSF decrease was 9.1 +/- 0.9 nl/min. Similar micropuncture techniques were used in proximal tubules of surface nephrons in these rats, which in comparison to the deep nephrons showed smaller feedback responses. The mechanism seems to be active at physiological nephron flow rates in both nephron populations. Thus, TGF can exert its effect on GFR of the whole kidney by acting in both deep and surface nephrons.     

The effect of experimental alterations in urine concentration on nephron filtration rate

Summary Experiments were performed to clarify the cause of the dependency of juxtamedullary nephron filtration rate (JN-GFR) on the diuretic state of the animal. Using the ferrocyanide technique of de Rouffignacet. al. [5] the distribution of nephron filtration rates was determined during selective modification of final urine osmolarity by papillary superfusion with concentrated or isotonic solutions. Papillary superfusion with a 2000 mosmolar solution led to a mean urine osmolarity of 1848±78 mOsm/l. JN-GFR displayed a mean increase of 66.6% over the superficial nephron filtration rate (SN-GFR). When the superfusion fluid was isotonic urine osmolarity averaged 754±53 mOsm/l and JN-GFR increased by a mean of only 26.3% over the SN-GFR. Using the micropuncture technique it was shown that SN-GFR in a given animal was not altered when the superfusion fluid was interchanged. We conclude therefore that the change in the percentage increase in GFR from superficial to juxtamedullary nephrons is caused by a change of juxtamedullary nephron filtration rate. Since plasma ADH concentration was not altered this effect appears to be elicited by the changed medullary solute concentration rather than by a vasomotor action of the antidiuretic hormone.This work was supported by the Deutsche Forschungsgemeinschaft.     

Détermination du taux individuel de filtration glomérulaire des néphrons accessibles et inaccessibles à la microponction

Résumé Nous présentons dans ce travail une modification de la technique de Hanssen qui permet de la rendre quantitative.Un indicateur glomérulaire marqué (ferrocyanure de sodium¹⁴C) est perfusé à des rats anesthésiés jusqu'à l'obtention d'une concentration plasmatique stable. Puis 20 l d'une solution à 10% de ferrocyanure non marqué sont injectés rapidement au dessus de l'artère rénale gauche. Quelques secondes plus tard, le pédicule rénal gauche est lié. Le ferrocyanure contenu dans le rein est alors précipité sous forme de bleu de Prusse insoluble, puis les tubules proximaux sont disséqués après macération. De la radioactivité contenue dans le néphron entre le glomérule et le précipité de ferrocyanure non marqué (radioactivité qui correspond donc au¹⁴C ferrocyanure filtré pendant un temps déterminé) et de la concentration plasmatique de cet indicateur, on déduit le débit de filtration (fg) du néphron considéré.Les résultats obtenus chez trois rats non diurétiques sont donnés à titre d'exemple. La fg de néphrons superficiels et profonds ayant une longueur moyenne de tubule proximal de 7,6 mm et 8,9 mm respectivement a été calculée à partir de l'équation de la droite de régression décrivant la variation de la fg en fonction de la longueur du tubule proximal: elle a été trouvée égale à 29,1 nl/min pour les néphrons superficiels et 40,1 nl/min pour les néphrons profonds.La validité de la technique est attestée 1. par le fait que la filtration glomérulaire totale du rein, calculée à partir des fg, est sensiblement identique à celle mesurée quelques minutes plus tôt (C _in 2. par le fait que les valeurs des fg ainsi que les corrélations anatomo-fonctionnelles rapportées sont identiques à celles obtenues par la technique de Hanssen, 3. enfin par le fait que les fg des néphrons superficiels sont semblables à celles habituellement mesurées par microponction.Notre technique conserve tous les avantages de la méthode de Hanssen, mais elle en supprime les inconvénients liés à l'hétérogénéité de distribution dans le rein de l'indicateur marqué puisqu'ici, au lieu d'être administré en une seule injection, le ferrocyanure marqué est perfusé à l'animal; de plus, elle permet une mesure quantitative des valeurs individuelles de fg même sur des reins anuriques.

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Determination of glomerular filtration rate of individual nephrons accessible and inaccessible to micropuncture

Summary We describe a modification of Hanssen's technique. Anesthetized rats were infused with a¹⁴C–Na-ferrocyanide solution. At equilibrium, 20 l of a 10% non labelled ferrocyanide solution were injected as a short pulse above the left renal artery. A few seconds later, the left renal pedicle was tied. Ferrocyanide contained within the kidney was precipitated as insoluble Prussian blue and the proximal tubules were microdissected after maceration. From the radioactivity contained within the nephron from the glomerulus to the precipitate of non labelled ferrocyanide (radioactivity which is due to the¹⁴C filtered during a given time) and from the¹⁴C plasmatic concentration, we deduced the single glomerular filtration rate (SGFR) of the nephron.Three non diuretic rats are given as example. The SGFR of superficial and juxtamedullary nephrons was respectively equal to 29,1 nl/min and 40,1 nl/min when calculated for the mean value of the length of their proximal tubules (respectively 7.6 mm and 8.9 mm) from the equation of the regression line which described the correlation between SGFR and the length of the proximal tubule.The reliability of the technique is supported 1. by the fact that the value of the GFR of the whole kidney calculated from SGFR's was the same asC _in measured just prior, 2. by the fact that SGFR values and the anatomo-physiological correlations were identical to those obtained with the Hanssen's technique, 3. and by the fact that the SGFR of superficial nephrons agree with most of those obtained with the micropuncture techniques.Most of the criticisms of Hanssen's technique, which arise from the observation that the bolus of labelled precipitate is sometimes inhomogenously distributed from one region of the kidney to another, are not valid here because instead of being injected as a pulse, the¹⁴C-ferrocyanide is infused continuously into the animal. Moreover, our technique allows measurements of SGFR's even in non urine forming kidneys.

Docteur en médecine, Attaché de recherche à l'Institut National de la Santé et de la Recherche Médicale.     

Single nephron glomerular filtration rate ratios of superficial,intercortical and juxtamedullary nephrons in rats during development

Summary In 20, 40 and 60-day-old rats the filtration rate was studied, using Baines modification of Hanssen's Na₄Fe(¹⁴CN)₆ method enabeling the determination of single nephron glomerular filtration rate (SNGFR) ratio between superficial (S), intercortical (I) and juxtamedullary (J) nephrons. The proximal tubule lengths were determined as well. A close correlation was obtained between age and S/I, I/J and S/J of proximal tubule lengths and between age and I/J, S/J¹⁴C-activities of ferrocyanide. Presented findings confirm the data on the increasing role of superficial nephrons in the course of postnatal development of rat.     

Single glomerular filtration rate of superficial and Juxta-medullary nephrons in the rat during different types of arterial hypertension

Summary The single nephron glomerular filtration rate (SNGFR) of superficial (S) and juxtamedullary (JM) nephrons were measured using¹⁴C-ferrocyanide infusion technique in rats under 3 different states of hypertension: acute hypertensions obtained either by bilateral carotid clamping (CC) or by contralateral renal ischemia (CI), and chronic Goldblatt hypertension. The juxtaglomerular index (JGI) was determined on the experimental kidneys.During acute hypertensions the JGI was normal, the granularity being more marked for the superficial than for the deep cortex. SNGFRs were higher in the JM (CC=39.2±3.4 SE nl/min; CI=41.0±4.5) than in the S (CC=30.3±2.5 CI=30.3±3.0) nephrons. These values are not different from those of normal rats. In the untouched kidney of Goldblatt rats the JGI was equal to zero. There was a general increase in SNGFRs. This increase was more marked for the S than for the JM nephrons, and the SNGFRs equalized in these two categories of nephrons (S=73.0±8.4; JM=74,7±8.2).From these observations, it is suggested that the renin content of the juxtaglomerular apparatus may play some role in the absolute value and intrarenal distribution of SNGFRs.This work was supported in part by a grant D.G.R.S.T. No. 7172 2726.Chargé de recherches à l'INSERM.     

Adaptive changes of juxtamedullary glomerular filtration in the remnant kidney

The participation of surviving juxtamedullary nephrons in the adaptive changes of glomerular filtration that occur in response to loss of functioning nephron mass was examined by direct micropuncture of the rat renal papilla. The solitary remnant kidney (RK) in rats with an 85% reduction of renal mass demonstrated strikingly elevated values for single nephron glomerular filtration rate (SNGFR) in both superficial (46.1±3.2 nl/min) and juxtamedullary (73.5±6.1 nl/min) nephrons in comparison to respective values observed in normal hydrophenic rats (superficial SNGFR=15.0±1.9nl/min,P<0.001, and juxtamedullary SNGFR=30.2±3.2 nl/min,P<0.001). In RK rats, the proximal portions of both superficial and juxtamedullary nephrons exhibited a marked increase in absolute fluid reabsorption as well as a markedly enhanced delivery of fluid to more distal portions of the nephron. These observations indicate that similar, not preferential, functional adaptations in glomerular filtration occur concommitantly in both superficial and juxtamedullary nephrons consequent to reduction of renal mass.     

Influence of water-diuresis or saline volume expansion on deep nephron tubuloglomerular feedback

We have recently demonstrated the existence of a tubuloglomerular feedback mechanism in juxtamedullary nephrons in rat kidneys during antidiuresis. In the present experiments, we have investigated the influence of water-diuresis on Munich Wistar rats and in homozygote Brattleboro rats. We have also observed the effect of saline volume expansion on the tubuloglomerular feedback of juxtamedullary nephrons in Munich Wistar rats. For comparison, the feedback mechanism was also studied in surface nephrons during water-diuresis in Munich Wistar rats. Measurements of flow rate in the descending limb of Henle and single nephron glomerular filtration rate (GFR) using micropuncture at the renal papilla were performed, while the ascending limb was microperfused at varying perfusion rates with a modified Ringer solution. In surface nephrons early proximal flow rate, single nephron GFR and stop-flow pressure was measured during microperfusion of the end-proximal loop. No significant changes were measured in surface nephrons during water-diuresis: the tubular flow rates, feedback responses, stop-flow pressure and stop-flow pressure changes were similar to those during anti-diuresis. In juxtamedullary nephrons, Henle loop flow rate increases during water-diuresis but the feedback-mediated flow and single nephron GFR response curves obtained during microperfusion were unaltered compared to controls. Together, these results indicate that the feedback could be more activated during water-diuresis than during control conditions. On the other hand, during saline volume expansion, reduced tubuloglomerular feedback sensitivity was found as shown earlier for surface nephrons. The reduction of tubuloglomerular feedback sensitivity therefore seems to be important in maintaining salt-, but not water-balance.     

Étude chez le rat des variations du débit individuel de filtration glomérulaire des néphrons superficiels et profonds en fonction de l'apport sodé

Résumé La distribution intrarénale des débits de filtration glomérulaire par néphron (fg) est étudiée en fonction de l'apport sodé chez trois groupes de rats: normaux, carencés en sodium et surchargés en sodium. Les fg ont été déterminées soit indirectement par la méthode de Hanssen soit grâce à une modification de cette méthode qui procure directement les valeurs absolues [23].Chez les rats normaux, la fg est égale à 27,9 nl/min pour les néphrons superficiels et à 38,5 nl/min pour les néphrons juxtamédullaires. Il n'existe pas de différence décelable entre les fg de nos rats sans sel et celles de nos rats normaux. Chez les rats surchargés en sel, les fg des néphrons superficiels et juxtamédullaires passent respectivement à 52,4 nl/min et à 52,7 nl/min.Au cours de nos surcharges sodées l'augmentation de filtration glomérulaire du rein résulte donc d'une augmentation de la fg de tous les néphrons. Celle-ci est cependant nettement plus marquée pour les néphrons superficiels et le rapport fg néphrons superficiels/fg néphrons juxtamédullaires qui est de 0,7 environ chez les rats normaux et sans sel, atteint 1,0 au cours de nos surcharges sodées. Ainsi dans cette dernière condition physiologique l'hétérogénéité fonctionnelle des néphrons disparaît. La variation des fg est discutée en fonction de ce que l'on sait de la variation de la distribution intrarénale de la rénine sous l'influence de l'apport sodé.

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Variations in glomerular filtration rate of single superficial and deep nephrons under various conditions of sodium intake in the rat

Summary The intrarenal distribution of single glomerular filtration rates (SGFR) was studied in rats previously fed a normal or a low sodium diet during antidiuresis, or in rats previously fed a high sodium diet during hypertonic saline diuresis. SGFR were determined either indirectly by Hanssen's technique, or directly by means of a modification of this technique which gives absolute values [23].In the normal rats, the mean value of SGFR of superficial and juxtamedullary nephrons was equal to 27.9 nl/min and 38.5 nl/min, respectively. There was no appreciable difference between SGFR in our normal and salt-deprived rats. In the salt-loaded rats, the mean value of SGFR of superficial and juxtamedullary nephrons reached 52.4 nl/min and 52.7 nl/min, respectively.Therefore, the increase of the GFR of the whole kidney during salt loading was due to an increase of SGFR of all the nephrons. However, the increase of SGFR was more important for the superficial ones and the ratio SGFR superficial nephrons/SGFR juxtamedullary nephrons which was 0.7 in the normal rats reached 1.0 in the salt-loaded rats, indicating that there was no more functional heterogeneity of nephrons during our salt loadings. The variation of SGFR is discussed in relation to the sodium dependent variation of the intrarenal distribution of renin observed by many authors.

Ce travail a été, en partie, présenté au 4ème Congrès International de Néphrologie, Stockholm 1969.     

Tubuloglomerular feedback and autoregulation of glomerular filtration rate in Wistar-Kyoto spontaneously hypertensive rats

Experiments were done in Wistar-Kyoto spontaneously hypertensive rats (SHR) to examine the efficiency of autoregulatory adjustments of kidney and nephron filtration rate (GFR) to acute changes in blood pressure (BP) over a broad blood pressure range. When BP of the SHR was reduced from 158±7 to 118 ±3 mm Hg by aortic clamping, kidney-GFR remained unchanged from 1.19±0.11 to 1.17±013 ml·min^–1·g^–1 kidney weight (KW), respectively. Single nephron GFR (SNGFR) measured at early distal tubule sites was similarly unchanged with the same BP change, 27.9±1.5 vs. 24.9±2.1 nl·min^–1·g^–1 KW (P>0.10). Proximal and distal estimates of SNGFR were significantly different from each other at high BP (7 nl·min^–1·g^–1,P<0.025), but were not different at low BP (2.0 nl·ml^–1·g^–1,P>0.10). Studies assessing tubuloglomerular feedback activity were done with orthograde perfusion of the loop of Henle using recollections of early proximal flow rate (EPFR) as an index of change of glomerular filtration rate. A change in perfusion rate from 0 to 45 nl·min^–1 induced a reduction in early proximal flow rate of 40.5 ±4.5%. Juxtaglomerular renin activity of superficial nephrons was 36.2±4.3 in the SHR, a value insignificantly different from 23.7±4.4 ng Angiotensin II amide·0.1 ml^–1·h^–1. 5 glomeruli^–1 in normal controls (P>0.05). The SHR appears to behave as a normal animal with respect to tubologlomerular feedback and autoregulatory renal vascular adjustments. Like normal rat models, the SHR demonstrated dependence on maintenance of distal filtrate delivery to achieve single nephron GFR autoregulation.Financial support for these studies and for Dr. Ploth were made available by funds from the Deutsche Forschungsgemeinschaft     

Number of nephrons in hypertrophic kidneys after unilateral nephrectomy in young and adult rats

Summary The number of functional nephrons in hypertrophied kidneys was determined in adult non diuretic rats which had been uni-nephrectomized either before 45 days (NY) or after 90 days (NO). This number was calculated by dividing the whole kidney GFR by the single nephron GFR, measured either by micropuncture or the¹⁴C-ferrocyanide infusion technique. Kidney weight was greater in NY rats (1.48±0.08 g SE) than in NO rats (1.23±0.10). In micropuncture experiments on NO rats the number of nephrones (34300±1600) was similar to that of normal adult rats. In NY rats this number was significantly greater (44100±1800,P<0.001).The ferrocyanide technique gave similar results (NO rats: 34800±2100; NY rats: 43900±3600) and indicated that the ratio of superficial to juxtamedullary SNGFR was not altered in the hypertrophied kidneys.The length of microdissected proximal tubules was increased in hypertrophied kidneys of both NY and NO rats and this increase affected thepars recta andpars convoluta equally.Single nephron GFR and F/P Inulin in late proximal and early distal tubules were similar in NO and NY rats.In conclusion, our results demonstrate that when uni-nephrectomy is performed on young rats, the compensatory hypertrophy of the remaining kidney is the result of an increase in both the size and the number of nephrons.     

Functional heterogeneity of nephrons

Summary Non-diuretic rats and saline diuretic psammomys received 0.05 ml¹⁴C Na ferrocyanide i.v. Their kidneys were frozen in vivo 8–10 sec later. The quantity of¹⁴C ferrocyanide precipitated as prussian blue (Hanssen) in the lumen of a microdissected proximal tubule was proportional to its glomerular filtration rate (gfr). Distance between dye front and glomerulus was proportional to mean flow velocity (v). Fractional water reabsorption at the dye front was calculated using gfr, v and luminal radius. There were large differences in gfr, v and fractional water reabsorption between superficial and deep nephrons. Published micropuncture data agrees quantitatively with our results. Glomerular volume, tubular length and luminal radius increased from superficial to juxtamedullary proximal tubules in both species. Filtration rate varied directly with glomerular volume suggesting an influence of capillary surface area on filtration. Tubular length and luminal radius correlated with gfr. Proximal water reabsorption rate correlated with luminal radius in psammomys but not in rat tubules. Water reabsorption by the entire proximal tubule decreased with length in rat tubules but increased in psammomys. The discrepancy may be due to differences in blood flow distribution which alter gfr and/or water reabsorption in superficial relative to deep nephrons.     

Technical problems in the micropuncture determination of nephron filtration rate and their functional implications

Summary The theory of a functional coupling between distal tubular fluid composition and glomerular filtration rate implies that the blockade of flow at a proximal site should lead to a marked increase of GFR. This potential alteration of steady state GFR was studied by comparing the influence of sampling from distal or proximal sites on the filtration rate of identical nephrons. During antidiuresis an average GFR of 25.2 nl/min±7.5 S.D. was found in distal collections, while proximally collected samples gave an average GFR of 34.5 nl/min±8.4 S.D. This difference of 9.3 nl/min is highly significant (p<0.001). During saline diuresis a mean nephron GFR of 41.6 nl/min±5.0 was found by distal sampling and of 45.3 nl/min±5.4 by proximal sampling (p>0.05). The proximal-distal difference in nephron GFR is interpreted to indicate the operation of a tubulo-glomerular feedback control system. Thus, a true steady-state GFR probably cannot be obtained by proximal fluid collection.Even in the presence of high intratubular pressures and unusually short oil blocks no evidence of sample contamination by retrograde fluid flow past an injected oil block was obtained.The application of a counter-pressure to the sampling pipette which has been recommended by Gertzet al. [5] as a means to standardize fluid collections, was found to lead to abnormally high intratubular pressures. The reason for this finding appears to be an unexpectedly high and inconstant tip resistance to flow during fluid flow into the pipette.     

Beschleunigte Natriurese und Diurese beim Hochdruck: Folge einer Resorptionshemmung in der Henleschen Schleife

Summary Exaggerated natriuresis and diuresis in chronic hypertension: Result of impaired fluid reabsorption in the loop of Henle.Micropuncture studies were performed in normotensive and chronically hypertensive rats (unilateral renal artery stenosis). Excretory and tubular function of the untouched kidney exposed to the high blood pressure (185 mm Hg) was investigated before and after i.v. 2.5% sodium chloride loading (0.1 ml/min) and compared to that of normotensive rats (98 mm Hg). The onset of diuresis and natriuresis was more rapid in the hypertensive rats than in the control group. Fractional sodium excretion of the hypertensive rats rose to 11% of the filtered load, while it reached only 3% in the controls. Total GFR and superficial single nephron GFR were elevated in both groups, but the increase in filtration rate occured earlier in the hypertensive group. Fractional sodium and water reabsorption in the proximal tubule decreased in both groups to the same extent. In the hypertensive rats, fractional water reabsorption along the loop of Henle was less than half of normal. The reduced fractional reabsorption in Henle's loop was already present in the control period and is thought to be the result of an increased medullary blood flow caused by the high blood pressure. Early distal TF/P-Inulin ratio declined from 2.8 to 1.9 in the hypertensive group and from 4.7 to 2.45 in the control group. In the normotensive group the reduced proximal reabsorption was partly compensated by an increased fractional reabsorption in distal tubules and collecting ducts. In contrast, there was a marked reduction of fractional water reabsorption in distal tubules of the hypertensive group. The combined inhibition of fractional reabsorption in the proximal tubule, in Henle's loop and in the distal tubule leads to the exaggerated natriuresis and diuresis in the hypertensive rats.

     

Development of the metanephros in the chick: maturation of glomerular size and nephron length

Summary In the avian kidney three nephron types may be identified: mammalian-type nephrons with long (MTN-I) and short (MTN-II) loops of Henlé, and reptilian-type nephrons (RTN). By the method of microdissection the maturation of the nephrons of domestic fowl kidney has been studied. From the 14th day of incubation it is possible to isolate the MTN-I which appear first; all three nephron types may be isolated after 18 days of incubation. The thin limb of Henlé's loop in MTN-I appears after hatching, and the length of this segment in 1-day-old chicks is 0.1–0.13 mm. In 60-day-old chicks its length has approximately doubled. The transition of the thin segment to the thick segment is situated in the descending part of Henlé's loop. In the course of development, the relative length of all nephron segments in MTN-I increases uniformly, while in MTN-II and in RTN the relative length of the proximal and distal convoluted tubules increases. At all stages of development, MTN-I are the longest among the three groups of nephrons and have the largest glomeruli. The comparison between developing avian and mammalian kidneys shows great similarities in the process of maturation in analogous nephron types in these two classes of vertebrates.     

Regulation of superficial nephron filtration rate by tubulo-glomerular feedback

Summary Possible regulation of glomerular filtration rate by tubulo-glomerular feedback from a late tubular site was studied in microperfusion experiments on rats. During perfusion of loops of Henle with varying flow rates and different perfusion solutions, filtration rate of the perfused nephrons was measured by total proximal fluid collection and inulin determination. During perfusion with isotonic Ringer's solution nephron filtration rate decreased significantly with increasing perfusion rates. Since proximal intratubular pressure was experimentally kept constant, this response must reflect decreased glomerular capillary pressure. Increasing the flow rate during perfusion with isotonic sodium sulfate or mannitol solutions was not associated with significant changes of filtration rate. Thus some correlate of the flow rate of normal loop of Henle fluid can affect filtrate formation. Such an effect may be mediated by the juxtaglomerular apparatus. Our results are consistent with the concept that the triggering signal is a function of the amount of distal sodium that is able to permeate the cell membrane at the receptor site rather than of distal intratubular sodium concentration.On leave from the Department of Physiology, University of Melbourne as recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

Development of glomerular filtration rate and electrolyte and osmolal clearance in the late-embryonic and newly hatched chicken

Summary Techniques have been developed for collection of urine in embryonic and newly hatched chickens for the purpose of studying the development of renal function.The reliability of EDTA-⁵¹Cr as a substitute for inulin-¹⁴C in the determination of GFR was studied. Since inulin and EDTA-⁵¹Cr clearances in the hatched chicken averaged 1.61±0.23 (S.E.) ml/min per kg body weight and 1.58±0.27 ml/min per kg body weight, respectively, EDTA-⁵¹Cr clearance was considered a suitable measure of GFR.GFR increased significantly in the first few days after hatching. Filtration rate was 0.068±0.008 (S.E.) ml/min per g kidney weight in the embryo and increased to 0.148±0.008 ml/min per g shortly after hatching. By nine days after hatching GFR had risen to 0.290±0.015 ml/min per g, a value comparable to that reported for the adult.Clearances of sodium, potassium, chloride and total osmolyte also increased with age. When these clearances were corrected for changing glomerular filtration rates the embryonic chicks were found to excrete a greater percentage of the filtered load. These results show that adult levels of glomerulo-tubular balance are not attained until after hatching.A preliminary report of this work has already been published [3].     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.