Functional and morphologic maturation of superficial and juxtamedullary nephrons in the rat.

The development of single nephron glomerular filtration rate (SNGFER) was studied in both superficial and juxtamedullary nephrons in rats in relation to concomitant morphologic maturation. These experiments were carried out in rats between 23 and 91 days of age (between 36 nad 275 g body weight) with the [14C]ferrocyanide infusion technique. 2. SNGFR of the superficial and juxtamedullary nephrons increased with body weight, glomerular volume and proximal tubular length. 3. The ratio SNGFR of the superficial (S) nephrons/SNGFR of the juxtamedullary (JM) nephrons rose from 0-60 in the 40-60 g rats to 0-84 in the adult rats, demonstrating the centrifugal functional maturation of the nephrons. 4. The S/JM ratio for both glomerular volume and tubular length was constant and averaged 0-72+/--0-12 and 0-81+/-0-05, respectively, indicating that while the increase in SNGFR was greater for S than for JM nephrons, this was not accompanied by concomitant disproportionate increases of glomerular volume and/or proximal tubular length between these nephron categories during development in the rat.     

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.     

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.     

Glomerular filtration rate and microsphere distributions in single nephron of rat kidney

In control non diuretic (ND) and in salt-loaded (SL) rats, both the microsphere technique and the 14C ferrocyanide infusion technique were used to determine the distribution of microspheres in single glomeruli and the SNGFR of the corresponding nephrons. A sample of microspheres with a diameter averaging 11.0 +/- 2.6 mu SD was selected from a 15 +/- 5 mu unlabelled batch. In each rat, three million of these microspheres were injected through the left carotid artery. The microspheres were directly counted under microscopic observation in the glomeruli of the nephrons which were microdissected to determine the SNGFR value. The number of microspheres per glomerulus for a given kidney generally varied from 0 to 8 and was independent to the SNGFR value. The diameter of the microspheres trapped was constant in all the animals. The mean number of microspheres for superificial (S) and juxtamedullary (JM) nephrons was, (ND); S = 1.99 +/- 0.48 SE., n = 5; JM = 3.02 +/- 0.51 SE, n = 5; P less than 0.02, (SL): S = 3.75 +/- 0.53 SE, n = 6; JM = 2.86 +/- 0.33 SE, n = 6; P less than 0.05. This distribution was directly related to that of SNGFR in ND rats (S = 39.0 +/- 6.1 SD and JM = 49.5 +/- 10.3 nl/min) but not in SL rats (S = 50.9 +/- 6.1 and JM = 66.9 +/- 10.0 nl/min). In conclusion, the microsphere technique described in the present paper, appears more suitable for investigating single glomerular blood flow since the number and the size of the microspheres trapped are directly determined at the level of the glomerulus.     

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.     

Time-dependent heterogeneity of filtration rate in the autoreguiating rat kidney

Experiments were performed to study the regulation of the single-nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephrons, as the left kidney of Sprague Dawley rats was submitted to a reduced arterial pressure of 70 mmHg by means of an aortic clamp. The SNGFR at different cortical levels was measured 0.5, 1, 5, 20 or 45 min after the reduction, in order to ascertain whether the effects of the regulatory mechanisms are modified with time. A Hanssen technique was used, which allows one determination of filtration rates per animal. At a renal arterial pressure (RAP) of 100 mmHg (= control animals) the SNGFR amounted to 20±1.2 and 23± 0.8 nlmin^-1–g^-1 kidney weight in the outer and inner cortical (OC, IC) nephrons. When RAP was further reduced to 70 mmHg, the autoregulation of SNGFR, determined after 0.5 min, was highly efficient for both OC and IC nephrons (19 ± 2.0, 23 ± 2.6). A prolonged reduction in RAP caused a gradual decline in SNGFR. The filtration rate measured after 5 min was 15 ±1.4 for OC and 20 ± 1.8 for IC nephrons. The decline was most pronounced for OC nephrons, which led to a fractional redistribution in favour of IC nephrons. Thus, SNGFR_IC/SNGFR_oc was 1.16± 0.065 when RAP was 100 mmHg and 1.41 ± 0.126 after 5 min with an RAP of 70 mmHg. It is well documented that suprarenal aortic occlusion is a powerful stimulus for the release of renin. This was manifested as an increase in the arterial pressure proximal to the aortic clamp. The fractional redistribution to IC nephrons and the loss of autoregulation, when the renal hypotension was sustained, may be an expression of the intrarenal mechanisms attempting to restore RAP. It is likely that the renin/angiotensin system is involved in these processes.     

Intra- and inter-nephron heterogeneity of gluconeogenesis in the rat: effects of chronic metabolic acidosis and potassium depletion

The intra- and inter-nephron heterogeneity of renal gluconeogenesis within rat proximal tubules and the effects of chronic metabolic acidosis and chronic potassium(K)-depletion were studied using isolated proximal tubules of rats by directly measuring glucose synthesized.The gluconeogenic activity from pyruvate and glutamine in control rats was almost limited to within the early proximal tubule (S1: 45.4±5.7 pmol/mm/60 min from pyruvate; 58.0±6.0 from glutamine). Very low, but detectable gluconeogenesis was observed in the middle portion of the proximal tubule (S2:9.9±2.2 from pyruvate; 4.8±1.1 from glutamine). The rate of glucose production in the terminal proximal tubule (S3) was negligible. Furthermore, gluconeogenesis from glutamine of superficial (SF) nephrons was significantly higher than that of juxtamedullary (JM) ones, whereas no difference was seen in gluconeogenesis from pyruvate.In acidotic and K-depleted rats, significant increase could be seen in S1 and S2, but the increase in S3 was not significant. By the serial determination in acidosis, the glucose production from both substrates was found to be the highest at the second 1 mm segment from the glomerulus, and it decreased downward along the proximal tubule. In acidosis, glucose production from both substrates in SF nephrons and that from glutamine in JM ones were elevated significantly compared with the control, but that from pyruvate in JM nephrons did not change.These results suggest that S1 of the SF nephron plays the most important role in gluconeogenesis in the control, whereas S1 of the JM nephron and S2 contribute to gluconeogenesis in acidotic and/or possibly K-depleted rats.     

Consistency of nephron filtration measurements by collection of total tubular fluid from different proximal sites

The stability of single nephron glomerular filtration rate (SNGFR) is assured by specific mechanisms such as the tubulo-glomerular feedback system and autoregulation. Studies on renal physiology rely heavily on the measurements of SNGFR, which are feasible only in animals. The measurement of SNGFR by collection of total tubular fluid may be influenced by the fall in intratubular hydrostatic pressure that may reflect the negative pressure applied to the sampling pipette. This effect may become more important with shortening of the distance between the sampling site and the Bowman space. We analysed this putative effect by performing collections of total tubular fluid from the late proximal (LP), and then from the early proximal (EP) segment of the same nephrons. In 128 paired collections LP-SNGFR averaged 35 (SEM 2) nl?·?min^?1, and was no different from the paired mean EP-SNGFR of 37 (SEM 2) nl?·?min^?1, P>0.179. Then EP- and LP- SNGFR were significantly correlated (r=0.77, P<0.001). As expected, the respective paired means of absolute and percentage reabsorptions, and those of collection rates were significantly different. The average SNGFR computed from each LP and EP paired measurement was significantly correlated with the simultaneously measured kidney glomerular filtration rate, GFR (r=0.60, P<0.0001). The ratio of GFR to SNGFR indicated the expected number of glomeruli. These data would indicate that the sampling site does not influence the measurement of SNGFR in the proximal tubule when the total fluid collection technique is correctly performed. They also exclude a time-dependent activation of the macula densa capable of upregulating SNGFR within the interval elapsing between the beginning of LP and the completion of EP collections, which in our study averaged 4.4 (SEM 0.1) min.     

Segmental analysis of the renal tubule in buffer production and net acid formation

Papillary and surface micropuncture in Munich-Wistar rats was used to assess the role of proximal segments of superficial and juxtamedullary (JM) nephrons, the distal tubule of superficial nephrons, and the terminal collecting duct in acid excretion. The relative role of these segments in ammonium production, bicarbonate reclamation, and net acid formation was assessed under hydropenic conditions and after a chronic acid load. In these two settings the proximal segment of both kinds of nephrons is the major site of ammonium production and bicarbonate reclamation. However, this segment's contribution to net acid formation was only significant during acidosis. On the other hand, segments beyond the distal tubule appear to be the major site of acid formation. In situ pH measurements were lower in these nephron segments and fell even more after the induction of an acidosis. Ammonia appears to enter fluid between the end of the distal tubule and the base of the collecting duct. In vivo pH measurements made near the bend of Henle's loop of JM nephrons were more alkaline than near the end of the proximal tubule of superficial nephrons. It is postulated that this difference in pH allows ammonium to dissociate, permitting the movement of ammonia out of the tubule lumen and into collecting duct fluid where it is protonated and, therefore, reentrapped. This process is enhanced by the ingestion of a chronic acid load.     

The influence of tubulo-glomerular feedback on the autoregullation of filtration rate in superficial and deep glomeruli

Single nephron glomerular filtration rate (SNGFR) of superficial and juxtamedullary nephrons were measured at normal and reduced perfusion pressure in the left kidney of young Sprague Dawley rats. Perfusion pressure was lowered by constricting the aorta proximal to the branching of the left renal artery. The influence of the tubulo-glomerular feedback mechanism on SNGFR was quantitated by measuring SNGFR during intact and interrupted urine flow to the macula densa region. By using a modified Hanssen technique, SNGFR was measured under free-flow conditions. In other experiments, the urine flow to the distal nephron was blocked by a micropuncture technique, which was used for collection of the tubular fluid for measuring the filtration rate. All nephron populations autoregulated SNGFR from 70–80 to 130 mmHg, which was the upper limit of this investigation, when urine flow throughout the nephron was intact. The autoregulation in this pressure range was lost when tubular fluid was prevented from reaching the distal nephron. It was shown that the influence of negative feedback on SNGFR by the macula densa mechanism at normal blood pressure is greater in deep nephrons than in superficial ones.     

Time-dependent heterogeneity of filtration rate in the autoregulating rat kidney

Experiments were performed to study the regulation of the single-nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephrons, as the left kidney of Sprague Dawley rats was submitted to a reduced arterial pressure of 70 mmHg by means of an aortic clamp. The SNGFR at different cortical levels was measured 0.5, 1, 5, 20 or 45 min after the reduction, in order to ascertain whether the effects of the regulatory mechanisms are modified with time. A Hanssen technique was used, which allows one determination of filtration rates per animal. At a renal arterial pressure (RAP) of 100 mmHg (= control animals) the SNGFR amounted to 20 +/- 1.2 and 23 +/- 0.8 nl X min-1 X g-1 kidney weight in the outer and inner cortical (OC, IC) nephrons. When RAP was further reduced to 70 mmHg, the autoregulation of SNGFR, determined after 0.5 min, was highly efficient for both OC and IC nephrons (19 +/- 2.0, 23 +/- 2.6). A prolonged reduction in RAP caused a gradual decline in SNGFR. The filtration rate measured after 5 min was 15 +/- 1.4 for OC and 20 +/- 1.8 for IC nephrons. The decline was most pronounced for OC nephrons, which led to a fractional redistribution in favour of IC nephrons. Thus, SNGFRIC/SNGFROC was 1.16 +/- 0.065 when RAP was 100 mmHg and 1.41 +/- 0.126 after 5 min with an RAP of 70 mmHg. It is well documented that suprarenal aortic occlusion is a powerful stimulus for the release of renin. This was manifested as an increase in the arterial pressure proximal to the aortic clamp.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics of the Glomerular Ultrafiltration in the Rat Kidney. An Experimental Study

The quantitative relation between the driving forces over the glomerular membrane and the glomerular plasma flow, on the one hand, and the single glomerular filtration rate (SNGFR), on the other, is still uncertain. Micropuncture measurements on Sprague-Dawley rats made it possible to calculate the net driving force over the glomerular membrane. The single glomerular plasma flow was determined from SNGFR and the single nephron filtration fraction (SNFF). The effective plasma flow was measured with PAH for total kidney and for superficial nephrons. The mean glomerular capillary pressure was found to be 62.6 mm Hg. The results indicate a net driving force of about 13 mm Hg at the distal end of the glomerular capillary. SNGFR was found to be 14.1 nl/min.100 g. SNFF amounted to about 0.27. The filtration fractions determined with the PAH method were in the same range. The results indicate a filtration disequilibrium, in contrast to those of Brenner et al. from measurements on a mutant Wistar rat strain. The filtration fractions seemed to be the same in all glomerular populations. It is clear that the SNGFR is pressure dependent. Our earlier findings of a nonautoregulation of the blood flow through the outer glomeruli were also confirmed.     

Developmental changes in nephron number, proximal tubular length and superficial nephron glomerular filtration rate of rats.

1. Post-natal development of single nephron glomerular filtration rate, superficial proximal tubular length, nephron number and kidney weight have been studied in Sprague Dawley and in Wistar rats. 2. Superficial tubular length is a non-linear function of body weight or age. There seems to be a rapid growth until animals weigh about 150 g in Wistar rats. In this strain, growth is slower thereafter. This difference is not as evident in Sprague Dawley rats. 3. Nephron numbers increase over the same period at which rapid tubular growth occurs. 4. Sprague Dawley rats have somewhat fewer, but longer, proximal tubules than do Wistar rats. 5. In all animals weighing more than 100 g, SNGFR is linearly related to weight. For younger, smaller Sprague Dawley rats, the same linearity holds over the age range studied--older than 20 days of age. In Wistar rats, SNGFR relative to weight is less in young animals. 6. By relating SNGFR to total kidney GFR, evidence is obtained that maturation of renal function also involves a greater increase in filtration by superficial than by juxtamedullary 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.     

Glomerular ultrafiltration in rabbits with superficial glomeruli

The determinants of glomerular ultrafiltration in superficial glomeruli of a strain of English cross-breed rabbits have been studied using micropuncture techniques. Mean arterial blood pressure in the anaesthetised rabbits was 70±2 mmHg. The glomerular filtration rate in the kidney prepared for micropuncture was 4.4±0.4 ml/min, the filtration fraction was 22±1% and renal blood flow was 33±3 ml/min, and these values were comparable to values in conscious rabbits. Glomerular capillary pressure (P _gc) averaged 31±1 mmHg, the single-nephron glomerular filtration rate (SNGFR) averaged 25±2 nl/min, and the mean ultrafiltration pressure (calculated using the whole-kidney filtration fraction) averaged 7±1 mmHg. A net positive pressure at the efferent end of the glomerular capillaries (4.4±0.9 mmHg) indicated that a state of filtration pressure disequilibrium existed, under the experimental conditions of this study, in rabbit glomeruli. The calculated glomerular ultrafiltration coefficient (K _f) was 0.08±0.01 nl s^–1 mmHg^–1. Thus, compared to the Munich-Wistar rat, SNGFR is lower in the rabbit. This reflects the substantially lower glomerular ultrafiltration pressure in the rabbit, although this was offset partially by a higher K_f.     

Kinetics of the glomerular ultrafiltration in the rat kidney. An experimental study.

The quantitative relation between the driving forces over the glomerular membrane and the glomerular plasma flow, on the one hand, and the single glomerular filtration rate (SNGFR), on the other, is still uncertain. Micropuncture measurements on Sprague-Dawley rats made it possible to calculate the net driving force over the glomerular membrane. The single glomerular plasma flow was determined from SNGFR and the single nephron filtration fraction (SNFF). The effective plasma flow was measured with PAH for total kidney and for superficial nephrons. The mean glomerular capillary pressure was found to be 62.6 mm Hg. The results indicate a net driving force of about 13 mm Hg at the distal end of the glomerular capillary. SNGFR was found to be 14.1 nl/min-100 g. SNFF amounted to about 0.27. The filtration fractions determined with the PAH method were in the same range. The results indicate a filtration disequilibrium, in contrast to those of Brenner et al. from measurements on a mutant Wistar rat strain. The filtration fractions seemed to be the same in all glomerular populations. It is clear that the SNGFR is pressure dependent. Our earlier findings of a nonautoregulation of the blood flow through the outer glomeruli were also confirmed.     

The existence of a tubulo-glomerular feedback mechanism in the Amphiuma nephron

A single nephron tubulo-glomerular feedback control of the glomerular filtration rate, which is known in mammlian animals, could be one way by which amphibians regulate the glomerular filtration rate (GFR). To investigate whether theAmphiuma means shows any sign of a tubuloglomerular feedback control, micropuncture experiments were carried out. Six different series of experiments were performed.In the first series, tubular stop-flow pressure (SFP) was measured during distal tubular perfusion with amphibian Ringer solution at a rate of 10, 25 and 50 nl/min. A significant decrease of SFP was found at the three perfusion rates compared to the controls. In the second group, single nephron glomerular filtration rate (SNGFR) was measured, while the distal tubule was perfused at 10, 25 and 50 nl/min. At a perfusion rate of 10 nl/min the SNGFR did not decrease, whereas at 25 and 50 nl/min it decreased significantly. In the third group the perfusion pipette was located in the proximal tubule and the nephron was perfused at 10, 25 and 50 nl/min, while at the same time the proximal tubular stop-flow pressure was measured. No reduction of SFP was found at a perfusion rate of 10 nl/min, while significant reductions were noted at rates of 25 and 50 nl/min. In the fourth group the SNGFR was measured in the distal tubule beyond the macula densa and in Bowman's space of the same nephron. No significant difference was found. In the fifth group, the glomerular capillary pressure (GCP) was measured before and after blockade of the tubular fluid flow. No significant difference was found between these two measurements.The sixth series deals with the changes occuring at the single nephron level by the tubulo-glomerular feedback control. The single nephron filtration fraction (FF) was determined from efferent arteriolar protein concentration with and without a feedback-induced reduction of the SNGFR. The FF values were not significantly different from one another. From these results and data from the other series, the afferent (R _aff) and efferent (R _eff) arteriolar resistances were calculated.R _eff did not change, whileR _aff increased significantly when a feedback stimulus was applied.These experiments indicate the existence of a tubuloglomerular feedback control which depresses the SNGFR and SFP by contracting the afferent arteriole.     

Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters

Renal phosphate reabsorption across the brush border membrane (BBM) in the proximal tubule is mediated by at least three transporters, NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Parathyroid hormone (PTH) is a potent phosphaturic factor exerting an acute and chronic reduction in proximal tubule phosphate reabsorption. PTH acutely induces NaPi-IIa internalization from the BBM and lysosomal degradation, but its effects on NaPi-IIc and Pit-2 are unknown. In rats adapted to low phosphate diet, acute (30 and 60 min) application of PTH decreased BBM phosphate transport rates both in the absence and the presence of phosphonoformic acid, an inhibitor of SLC34 but not SLC20 transporters. Immunohistochemistry showed NaPi-IIa expression in the S1 to the S3 segment of superficial and juxtamedullary nephrons; NaPi-IIc was only detectable in S1 segments and Pit-2 in S1 and weakly in S2 segments of superficial and juxtamedullary nephrons. PTH reduced NaPi-IIa staining in the BBM with increased intracellular and lysosomal appearance. NaPi-IIa internalization was most prominent in S1 segments of superficial nephrons. We did not detect changes in NaPi-IIc and Pit-2 staining over this time period. Blockade of lysosomal protein degradation with leupeptin revealed NaPi-IIa accumulation in lysosomes, but no lysosomal staining for NaPi-IIc or Pit-2 could be detected. Immunoblotting of BBM confirmed the reduction in NaPi-IIa abundance and the absence of any effect on NaPi-IIc expression. Pit-2 protein abundance was also significantly reduced by PTH. Thus, function and expression of BBM phosphate cotransporters are differentially regulated allowing for fine-tuning of renal phosphate reabsorption.     

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.