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].     

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.     

Balance between tubular flow rate and net fluid reabsorption in the proximal convolution of the rat kidney

Summary In rats with hereditary Diabetes insipidus (Brattleboro strain) proximal fluid reabsorption was studied during spontaneous variations of GFR. Independent of kidney weight and arterial blood pressure total kidney GFR varied between 0.35 ml/min×gKW and 1.8 ml/min×gKW, while single nephron filtrate showed a variation between 18 nl/min×gKW and 66 nl/min×gKW. End-proximal TF/P inulin of 78 fluid samples did not correlate with filtration rate and averaged 2.38±0.55 S.D. Also, proximal transit time was independent of filtration rate with a mean of 9.7 sec±1.1 S.D. These results imply a direct correlation between mean luminal radius and filtration rate, which was demonstrated by microphotography of the renal surface.Our data show that complete glomerulo-tubular balance in the proximal tubule exists during spontaneous variations of glomerular filtration rate. In support of the hypothesis ofGertz [4,6] the lateral net fluid flux was found to be linearly dependent upon tubular surface area. In addition, intratubular volume changed in direct proportion to single nephron filtrate. The present results are interpreted to further strengthen the assumption of a critical influence of tubular geometry on proximal fluid reabsorption during spontaneous variations of GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Micropuncture studies on the dog kidney

Summary Micropuncture studies were carried out on the dog kidney in order to delineate the response of micropuncture parameters to changes in blood pressure within and below the autoregulatory range. By the use of chloralose anaesthesia and carotid sinus denervation elevations in systemic blood pressure were induced, while the use of Regitine permitted the induction of lower BP levels both in the lower part of the autoregulatory range and to frankly hypotensive levels. The results indicate a constancy of intratubular function (TF/P inulin, transit time, single nephron GFR, intratubular pressure) so long as blood pressure remained within the autoregulatory range, supporting the concept of a preglomerular site for autoregulation. During hypotension the single nephron GFR decreased, the transit time was prolonged, but the end proximalTF/P inulin did not change significantly. These changes in tubular function corresponded to a fall in total GFR, RBF, and filtration fraction. The fall in single nephron GFR was greater than the corresponding fall in total GFR suggesting that during hypotension the filtrate of the punctured superficial nephrons is less well protected than that of other nephrons in the dog kidney.Supported in part by a Medical Research Fellowship of the Medical Research Council of Canada.     

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.     

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.     

The effect of saline infusion and hemorrhage on glomerular filtration pressure and single nephron filtration rate

Summary Single nephron filtration rate (GFRs) and effective glomerular filtration pressure (EFP) measured as the difference between intratubular stop-flow (SFP) and free-flow pressures (FFP), were determined in control rats and following saline infusion or hemorrhage. Infusion of isotonic or 4% NaCl increased EFP and GFRs without significantly affecting TF/P inulin. These findings could not be related to changes in arterial blood pressure. Controlled bleeding produced a marked decrease in EFP and in GFRs, again without significant change in TF/P-inulin. In both infusion and hemorrhage the change in GFRs was disproportionately greater than the change in EFP. Analysis of the components of the filtration process suggests that elevation of EFP is attended by an increase in permeability of the filtering membrane. This sensitive dependence of GFRs upon EFP, combined with a demonstrated constancy of total kidney GFR (GFR_T) over a wide range of urine concentrations and flow rates, connotes a close regulation of EFP in this experimental animal.Supported by Deutsche Forschungsgemeinschaft.     

The effects of chronic papillary necrosis on acid excretion

Complete papillary necrosis in rats can be induced within 1 month following a single injection of 2-bromoethylamine hydrobromide (BEA) (50 mg, i.v.). Utilizing a combination of clearance and balance techniques the effects of complete absence of the papilla was examined as regards urinary acidification, whole kidney glomerular filtration rate (GFR), single nephron GFR, and morphology. Whole kidney GFR was not different from control, however, the percent filtering juxtamedullary nephrons was markedly diminished (87.2±2.1 vs. 31.5±3.6% filtering, control vs. BEA, respectively,P<0.001) and significantly reduced in the superficial nephrons (80.6±3.6 vs. 62.2±6.1% filtering, control vs. BEA, respectively,P<0.05). There was a significant decrease in juxtamedullary single nephron GFR and an increase in the superficial single nephron GFR as assessed by the quantitative Hanssen's technique in the animals with chronic papillary necrosis. Complete papillary necrosis was associated with normal arterial bicarbonate concentration, pH, and plasma electrolyte concentrations. At the same degree of acidemia (induced by NH₄Cl administration) minimal urinary pH, ammonium excretion, and titratable acid excretion were not different than seen in age matched controls. The response to Na₂SO₄ infusion and phosphate infusion was the same in both groups of animals. The urineblood (U-B)pCO₂, an index of urinary acidification, was identical in BEA and control animals. Scanning electron microscopy showed scarring of the juxtamedullary glomeruli one month after BEA. The papilla was sloughed and lying free in the renal pelvis in every experimental animal. These data demonstrate that complete papillary necrosis is not associated with acidosis nor a defect in urinary acidification.     

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.     

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.     

Resetting of tubulo-glomerular feedback sensitivity by dietary salt intake

Summary Tubulo-glomerular feedback participates in the regulation of superficial nephron filtration rate, SN-GFR [13,29,30,32]. In the present experiments we investigated the possibility that the feedback response is modulated by salt intake. Five groups of rats were pretreated with diets containing different intake. Five groups of rats were pretreated with diets containing different amounts of sodium chloride in either food or drinking water. Estimated NaCl intake ranged from about 0.5 to 12 mEq per day and rat. Feedback response was tested in individual nephrons by comparing SN-GFR's derived from either distal tubular segments (i.e. with the macula densa region being perfused at normal rates) or end-proximal segments (i.e. with the flow in the macula densa region being acutely reduced). In accordance with earlier observations [8, 28], proximal SN-GFR exceeded the distal value in salt-deprived and control animals by 8.7 nl/min±8.6 (P<0.05) and 7.6 nl/min±5.4 (P<0.001) respectively. In contrast, rats supplied with 6, 11, or 12 mEq Na/day showed a proximal-distal SN-GFR difference of 1.4 nl/min ±8.5 (P<0.05), 1.2 nl/min±6.7 (P>0.05), and 4.6 nl/min±8.8 (P<0.001). Thus, elevation of NaCl intake either abolishes or diminishes feedback sensitivity in the subnormal flow range. We conclude that tubulo-glomerular feedback sensitivity is reset when sodium chloride intake is altered.Work performed during tenure of an Alexander von Humboldt-Dozentenstipendium.     

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.     

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.     

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.     

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.     

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.     

Filtration in surface glomeruli as regulated by flow rate through the loop of henle

Summary A new pressure transducer microperfusion system has been used to measure quantitatively SN GFR, early proximal free flow pressure and stop flow pressure of varying flow rates through the loop of Henle in the range of 0 to 50 nl/min. Perfusing the loop with an isoosmolal artificial tubular fluid at physiological flow rates SN GFR was 19.9±1.1 and 27.7±1.0 nl/min in two different strains of antidiuretic rats. SN GFR increased when loop perfusion was interrupted. The question whether a feedback control mechanism of SN GFR is operative in the rat kidney was evaluated in further experiments in which early proximal tubular pressure was measured in functionally isolated proximal convolutions in vivo under conditions of constant flow as well as stopped flow. Experiments in which perfusion rate through the loop of Henle was varied demonstrated the existence of a feedback signal which originates downstream of the late proximal convolution and which affects filtration into individual early proximal segments. This feedback mechanism exhibited an asymmetrical behaviour: Elevation of loop perfusion above the control value resulted in an early proximal pressure drop, under simulated free flow conditions as well as under stop flow conditions. In contrast lowering of perfusion rate below the predetermined physiological value had no significant effect on early proximal pressures.Index of Abbreviations FFP free flow pressure - P _a blood pressure - P _G mean glomerular capillary pressure - PCT proximal convoluted tubule - P _tub intratubular hydrostatic pressure - SFP stop flow pressure - SN GFR single nephron glomerular filtration rate - TF tubular fluid - TF/P concentration ratio between tubular fluid and plasma - V_(TF) collected volume of tubular fluid, flow rate Supported by Deutsche ForschungsgemeinschaftParts of the present work have been presented at the following meetings: Int. Symp. on Renal Handling of Sodium, Brestenberg1971; Workshop of Renal Micropuncture Techniques, Yale University 1971; Int. Congress of Nephrology, Mexico City 1972.     

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.     

Effects of prostaglandin E2 on excretion and reabsorption of sodium and fluid in rat kidneys (micropuncture studies)

Summary The effects of i.v. infusions of Prostaglandin E₂ on renal excretion of sodium and fluid were investigated in rats. Increasing diuresis was observed at infusion rates from 10 to 100 ng/min·100 g BW. Higher rates depressed the arterial blood pressure and urinary excretion rates. At 100 ng PGE₂/min·100 g BW urinary flow rate increased approximately 3 times and sodium excretion approximately 8–10 times above the control level. The urine/plasma concentration ratio of Na averaged 1.7 compared with 0.5 in controls. Potassium excretion, however, was only slightly enhanced.The effects on sodium and fluid excretion were not correlated with changes of total kidney GFR. Single nephron GFR of superficial nephrons remained unchanged during the PGE₂ infusion.Fractional proximal reabsorption of sodium and fluid, calculated from endproximal tubular fluid/plasma concentration ratios of Na and Inulin, were not inflenced by PGE₂. Transtubular net movements, calculated from split drop half time, were not significantly affected, too. Tubular transit time, however, was shortened, and fractional proximal reabsorption was decreased, when calculated fromt1/2 andT. This, too, indicates thatt1/2 andT do not always sufficiently define the fractional reabsorption.The normal decrease of the TF/P ratio of Na along the distal convolution is reduced under the influence of PGE₂. Approximately 2% of the filtered Na remain unreabsorbed in the distal convolution in addition to the amount found in controls. The high Na concentration in the final urine is established in the collecting ducts by an ADH like action.Preliminary reports of the results were presented in part at the 33rd meeting of the Deutsche Pharmakologische Gesellschaft in Heidelberg 1970.