Micropuncture method for the determination of nephron filtration rate

Summary Two possible artifacts may explain the phenomenon that nephron GFR (N-GFR) measured by distal tubular puncture is smaller than that measured by proximal tubular puncture: a loss of the inulin-like substance used in this laboratory (polyfructosan) from the tubular lumen or unreliable distal punctures. To test these possibilities (a) known amounts of polyfructosan were injected into the proximal tubule and the percentage recovery from the distal tubule measured, (b) N-GFR was measured by distal puncture, subsequently by recollection from the same site and finally by a proximal puncture.On the average, 98.5±7.5% of the proximally injected polyfructosan was recovered from the distal tubule. This is not significantly different from 100% (p>0.1) and demonstrates that proximal tubule and loop of Henle are impermeable to polyfructosan. The ratio between the N-GFR measured by a distal puncture and that measured by subsequent recollection was 1.016±0.096 and not significantly different from 1.000 (p<0.20), demonstrating the reliability of distal tubular puncture. The mean distal N-GFR of 27.9±5.3 nl/min was significantly smaller (p<0.001) than the proximal N-GFR of 35.1±8.0 nl/min. The existence of the proximal-distal N-GFR difference thus is confirmed and two possible artifacts eliminated. The best explanation remains the operation of a tubulo-glomerular feedback mechanism.A current point of dispute is the effect of alterations in intratubular pressure (ITP) on N-GFR. Collection of tubular fluid at ITPs below the previously measured free flow pressure (FFP) resulted in a change of N-GFR of 0.45 nl/min· cm H₂O. In contrast, fluid collection at ITPs greater than the FFP resulted in a change of N-GFR of 1.48 nl/min· cm H₂O. We conclude that although N-GFR is sensitive to ITP changes in both directions, pressure decreases are of little practical importance for the determination of N-GFR whereas intratubular pressure increases are to be avoided.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.     

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.     

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.     

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.     

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.     

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.     

Effects of acetylcholine on glomerular sieving of macromolecules

Summary Using a new biomathematical model recently proposed to calculate, from glomerular sieving data for PVP¹²⁵I, the pores radius (r) and the total area per unit of path length ( ) i.e. the parameters characterising the permeability of an ideal isoporous equivalent membrane, a mean value for the effective glomerular filtration pressure (GFP _e ) in the dog has been derived from Poiseuille's law.The effects of the intra-arterial perfusion of acetylcholine have been studied. As a meanr decreased by 5%, decreased by 35% while GFP _e increased by 60% in the perfused kidney. The same effects have been noticed but less pronounced in the controlateral kidney. These changes are accompanied by an increase in effective renal plasma flow but without modification of glomerular filtration rate (GFR).The significance of these results as far as GFR autoregulation is concerned, is discussed.Supported by the National Foundation for Medical Research-Grant 1197-Belgium.     

Measurement of the glomerular filtration pressure from sieving data for macromolecules

Summary Equations describing restricted filtration and diffusion of molecules in solution through porous membranes, macromolecular gels and capillary walls have been formulated by Pappenheimer; Renkin; and Landis and Pappenheimer. These formulations allow to calculate the radius of pores,r, (supposed cylindrical) and their total area per unit of path length: .In this study, they have been applied to characterize the glomerular sieve, starting from sieving data for PVP¹²⁵I.From the mean values forr and , supposing the membrane isoporous, the effective glomerular filtration pressure (GFP) was derived, applying Poiseuille's law. was 30(±2.2) mm Hg in dogs (n=20), and 19.6(±1.9) in humans (n=11).The isoporous model however does not account for the passage in the urine of comparatively large amounts of molecules with a radius higher than 41 Å.Assuming a lognormal distribution of pore radii allows a quite satisfactory adjustment of calculated and experimental values for sieving coefficients in a larger range of molecular radii (23 to 79 Å).This assumption necessitates to compute the value for GFP simultaneously to those characterizing the distribution (median and standard deviation). The values for GFP obtained by this method are slightly lower than [27.1(±2.8) mm Hg], but closely correlate with, those derived supposing the membrane isoporous in dogs. In humans was 11.7(±1.7) mm Hg. However the sieving coefficients higher than 0.65 have to be discarded from the calculations on which rests the choice of the final value for . The reasons for the discrepancies between experimental and calculated values for sieving coefficients close to 1 are discussed by light of recent studies on sieving processes and membrane permeability.Supported by the Belgian Found for medical research (grant n^o 1197 and n^o 1215).     

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.     

Function of juxtamedullary nephrons in normotensive and chronically hypertensive rats

Summary The function of juxtamedullary nephrons was investigated by micropuncture of long loops of Henle at the exposed papilla in normal rats and in the untouched kidney of rats with experimental hypertension (unilateral Goldblattclip). With increasing blood pressure (range from 90–190 mm Hg) a continuous rise in juxtamedullary single nephron glomerular filtration rate was observed. Juxtamedullary single nephron GFR averaged 60×10^–6 ml/min/g K.W. in the control group (mean arterial blood pressure 116 mm Hg) and 114×10^–6 ml/min/g K.W. in the hypertensive group (mean arterial blood pressure (164 mm Hg). There was no change in superficial single nephron GFR (30×10^–6 ml/min/g K.W.) but a slight increase in total kidney GFR from 1.07 to 1.28 ml/min g K.W. In both the normotensive and the hypertensive animals, tubular fluid-to-plasma (TF/P) inulin ratio and intratubular flow rate in the descending limb of the long loops of Henle were not statistically different from those found in the ascending limb. Intratubular flow rate in the hypertensive rats was twice as high as in the controls; the mean TF/P inulin ratios in the two groups did not differ from each other. Appearance time of lissamine green in the long loops of Henle and in the collecting ducts was shortened in the hypertensive animals. It is concluded that there is no autoregulation of glomerular filtration rate in juxtamedullary nephrons. The increased juxtamedullary GFR may contribute to the elevated urinary excretion of the unclipped kidney in hypertensive rats.This paper was presented before the German Physiological Society, Mainz, March 1969 [11].     

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.     

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.     

Reduction of the glomerular filtration rate by the efferent blood from a kidney taken from a previously dehydrated dog

Summary The two kidneys of one dog were perfused separately with the same blood pool and at a constant arterial pressure. After the control periods, one of the kidneys was replaced by another one taken from a dehydrated dog. The presence of the dehydrated kidney resulted in significant and almost immediate decreases of creatinin clearance, urine flow and sodium excretion by the contralateral kidney, without any change in the overall renal blood flow. These changes disappeared, after the removal of the dehydrated kidney. They were not observed if the dehydrated kidney was replaced either by a kidney taken from a salt-depleted, non water-deprived dog, or by a simple arterio-venous shunt. These results suggest that in the status of dehydration, the kidney releases some humoral material which might be responsible for the decrease of the measured GFR (C creat) perhaps by the way of permeability changes.     

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery

OBJECTIVE:

Pneumoperitoneum during laparoscopy results in transient oliguria and decreased glomerular filtration and renal blood flow. The presence of oliguria and elevated serum creatinine is suggestive of acute renal injury. Serum cystatin C has been described as a new marker for the detection of this type of injury. In this study, our aim was to compare the glomerular filtration rate estimated using cystatin C levels with the rate estimated using serum creatinine in patients with normal renal function who were undergoing laparoscopic surgery.

METHODS:

In total, 41 patients undergoing laparoscopic cholecystectomy or hiatoplasty were recruited for the study. Blood samples were collected at three time intervals: first, before intubation (T1); second, 30 minutes after the establishment of pneumoperitoneum (T2); and third, 30 minutes after deflation of the pneumoperitoneum (T3). These blood samples were then analyzed for serum cystatin C, creatinine, and vasopressin. The Larsson formula was used to calculate the glomerular filtration rate based on the serum cystatin C levels, and the Cockcroft-Gault formula was used to calculate the glomerular filtration rate according to the serum creatinine levels.

RESULTS:

Serum cystatin C levels increased during the study (T1 = T2<T3; p<0.05), whereas serum creatinine levels decreased (T1 = T2>T3; p<0.05). The calculated eGlomerular filtration rate-Larsson decreased, whereas the eGlomerular filtration rate-Cockcroft-Gault increased. There was no correlation between cystatin C and serum creatinine. Additionally, Pearson''s analysis showed a better correlation between serum cystatin C and the eGlomerular filtration rate than between serum creatinine and the eGlomerular filtration rate.

CONCLUSION:

This study demonstrates that serum cystatin C is a more sensitive indicator of changes in the glomerular filtration rate than serum creatinine is in patients with normal renal function who are undergoing laparoscopic procedures.     

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].     

Glomerular filtration changes during renal artery infusion of various hypertonic solutions in the dog

Summary Effects of renal artery infusion of hypertonic equiosmolar solutions of NaCl, Na₂SO₄, urea, glucose and mannitol on the glomerular filtration rate (GFR) were studied in anesthetized dogs. GFR was determined as a product of the renal plasma flow—calculated from directly measured renal blood flow and hematocrit—and the extraction ratio of exogenous creatinine (RPF·E _cr).Hypertonic solutions of urea, glucose and mannitol depressed GFR while NaCl and Na₂SO₄ were without significant effect. The change in filtration was a linear function of the inhibition of the net absolute tubular reabsorption of water (T _{H 2}O) caused by hypertonic infusions. This relation was observed with all the infusates except Na₂SO₄ which depressed totalT _{H 2}O but did not affect GFR. It is suggested that a definite inhibition of proximal reabsorption, probably absent with Na₂SO₄ infusion, determines the fall in GFR in osmotic diuresis.     

Single nephron filtration,luminal flow and tubular fluid reabsorption along the proximal convolution and the pars recta of the rat kidney as influenced by luminal pressure changes

Summary Intratubular pressures were measured in free flow and after blockade of tubular flow at different distances from the glomerulum in the kidney of Wistar rats. Free flow pressure wasffp=13.3 ±2.5 Torr and stop flow pressuresfp=41.7±3.8 Torr. With increasing distance of the blockade from the glomerulum the intratubular pressure decreased being 22.4±2.1 Torr, when the tubule was blocked at the end of the pars recta. In a second series single nephron filtration rate (gfr) and late proximal flow rates were measured at different intratubular pressures. Free flowgfr _f was 26.5±5.9 nl/min and . The difference of these flow rates divided by tubular length results in a local reabsorption rate ofC=2.9±0.9 nl/min·mm in the proximal convolution. In the pars recta local reabsorption rate was 1.0±0.3 nl/min·mm. In the proximal convolutionC increased with increasing intratubular pressure: ΔC/Δitp=(2.7±1.2)·10⁻² nl/min·mm·Torr. Filtration was in disequilibrium in these animals under all conditions examined, hydraulic filtration conductance wasK=1.2±0.4 nl/min·Torr. Modified methods have been used for intratubular pressure and for flow rate measurements in order to reduce experimental procedure. It is shown, that fractional reabsorption, calculated on the basis of pressure measurements, is a good approximation to results usually obtained by inulin measurements.     

Correlation between single nephron glomerular filtration rate and filtration area in superficial glomeruli of developing rats

Single nephron glomerular filtration rate (SNGFR) was correlated to the area of the glomerular basement membrane (GBM) determined by stereological techniques in rats between 20 and 40 days of age. Single nephron glomerular filtration rate increased 8.4 times in parallel with a twofold increase in GBM area. The much greater postnatal increase in SNGFR than in GBM area demonstrates that the increase in GBM area cannot account for the entire increase in SNGFR. Instead a combination of other factors influencing SNGFR most likely determines the largest part of the increase in SNGFR during this period. Thus, the drop in vascular resistance known to occur during maturation will increase the renal blood flow and may cause the filtration process to turn from a state of filtration equilibrium to or close to disequilibrium, thereby increasing GFR. Additional increase in GFR may be due to an increased net driving force for filtration and/or changed hydraulic permeability.     

Influence of hepatic innervation on renal glomerular filtration rate

Electrical stimulation of perivascular portal nerves leads to rapid, transient increase of renal glomerular filtration rate (GFR) and of urinary flow rate ( ). In contrast, perivascular stimulation at the vena cava inferior does not significantly alter GFR and . Spinal transfection at the thoracocervical junction does not significantly modify the effect of periportal nerve stimulation. Infusion of the -adrenergic agonist phenylephrine (20 nmol/min) into the superior mesenteric vein increases GFR and , whereas infusion of identical amounts of phenylephrine (20 nmol/min) into the jugular vein does not significantly alter GFR or . The observations indicate that -adrenergic innervation of the liver modifies renal function.     

Studies on the mechanism of reduction in glomerular filtration rate after benzolamide

In previous studies, we have shown that benzolamide, a carbonic anhydrase inhibitor with diuretic activity confined primarily to the proximal tubule, causes a significant reduction in nephron filtration rate by increasing afferent and efferent arteriolar vascular resistance [30], possibly through an activation of tubuloglomerular feedback mechanism. The present studies were designed to determine if infusion of 1-sar, 8-ala angiotensin II, an angiotensin II receptor antagonist (AIIA) could prevent and reverse the vasoconstriction and resulting reduction in SNGFR with benzolamide. Benzolamide administration to hydropenic rats decreased SNGFR by 5.0±1.3 nl/min and AIIA infusion in these rats completely restored SNGFR to the control, prebenzolamide values. These results occurred when SNGFR was measured in both proximal and distal tubules. In another group of hydropenic rats prior AIIA infusion completely prevented any alteration in SNGFR with benzolamide administration (33.0±2.8 vs. 32.3±1.5 nl/min). Benzolamide administration did increase the late proximal tubular flow rate during AIIA infusion (17.2±1.1 to 23.4±1.1 nl/min,P<0.01), demonstrating that AIIA did not act by preventing the diuretic action of benzolamide in the proximal tubule. AIIA infusion alone did not alter control SNGFR or nephron plasma flow, suggesting that the effect of AIIA was not that of a non-specific vasodilator. These studies suggest that the renal vasoconstriction and reduction in SNGFR which results from benzolamide administration is mediated by the local action of angiotensin II.