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Dromedary camels can survive and reproduce in desert areas. The unique anatomical structure of the kidney enables the camel to prevent water loss. The present study aimed to investigate the ultrastructure of the peroxisomes in the normal kidney of the adult dromedary camel. Tissue samples were taken from the cortex and outer medulla of the kidney of eight camels. The samples were then processed for histological and ultrastructural investigations. The epithelial cells of the proximal tubules displayed peroxisomes with varying sizes and shapes. The peroxisomes were observed in either dispersed or clustered arrangement. Each peroxisome exhibited a homogenous matrix enveloped by a single membrane. Several peroxisomes exhibited one or more dark marginal plates that were always strongly associated with the smooth endoplasmic reticulum. The intensity of the peroxisomal matrix differed significantly, either within the same cell or across different cells. The intensity was light or dark, with a few peroxisomes presenting a similar intensity to that of the mitochondria. Some peroxisomes contained nucleoids within their matrix. The peroxisomes in the first and second sections of proximal convoluted tubules were scattered and primarily located in the region between the microvilli and the underlying mitochondria. The peroxisomes in the third region were abundant and frequently aggregated in clusters throughout the cytoplasm. In the fourth region, the number of peroxisomes was low. The proximal straight tubule had a limited quantity of peroxisomes. In conclusion, peroxisomes in the proximal tubule in kidney of normal dromedary camel were similar in shape and size to other mammals; however, heterogeneity exists as a result of differences in species-specific peroxisomal proteins. Peroxisomes are suggested to be a major source of metabolic energy and act as hydrogen peroxide (H 2 O 2 ) scavengers, resulting in the release of water and oxygen., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Ca 2+ is an important second messenger that translates extracellular stimuli into intracellular responses. Although there has been significant progress in understanding Ca 2+ dynamics in organs such as the brain, the nature of Ca 2+ signals in the kidney is still poorly understood. Here, we show that by using a genetically expressed highly sensitive reporter (GCaMP6s), it is possible to perform imaging of Ca 2+ signals at high resolution in the mouse kidney in vivo. Moreover, by applying machine learning-based automated analysis using a Ca 2+ -independent signal, quantitative data can be extracted in an unbiased manner. By projecting the resulting data onto the structure of the kidney, we show that different tubular segments display highly distinct spatiotemporal patterns of Ca 2+ signals. Furthermore, we provide evidence that Ca 2+ activity in the proximal tubule decreases with increasing distance from the glomerulus. Finally, we demonstrate that substantial changes in intracellular Ca 2+ can be detected in proximal tubules in a cisplatin model of acute kidney injury, which can be linked to alterations in cell structure and transport function. In summary, we describe a powerful new tool to investigate how single cell behavior is integrated with whole organ structure and function and how it is altered in disease states relevant to humans.

Background: The kidney proximal convoluted tubule (PCT) reabsorbs filtered macromolecules via receptor-mediated endocytosis (RME) or nonspecific fluid phase endocytosis (FPE); endocytosis is also an entry route for disease-causing toxins. PCT cells express the protein ligand receptor megalin and have a highly developed endolysosomal system (ELS). Two PCT segments (S1 and S2) display subtle differences in cellular ultrastructure; whether these translate into differences in endocytotic function has been unknown., Methods: To investigate potential differences in endocytic function in S1 and S2, we quantified ELS protein expression in mouse kidney PCTs using real-time quantitative polymerase chain reaction and immunostaining. We also used multiphoton microscopy to visualize uptake of fluorescently labeled ligands in both living animals and tissue cleared using a modified CLARITY approach., Results: Uptake of proteins by RME occurs almost exclusively in S1. In contrast, dextran uptake by FPE takes place in both S1 and S2, suggesting that RME and FPE are discrete processes. Expression of key ELS proteins, but not megalin, showed a bimodal distribution; levels were far higher in S1, where intracellular distribution was also more polarized. Tissue clearing permitted imaging of ligand uptake at single-organelle resolution in large sections of kidney cortex. Analysis of segmented tubules confirmed that, compared with protein uptake, dextran uptake occurred over a much greater length of the PCT, although individual PCTs show marked heterogeneity in solute uptake length and three-dimensional morphology., Conclusions: Striking axial differences in ligand uptake and ELS function exist along the PCT, independent of megalin expression. These differences have important implications for understanding topographic patterns of kidney diseases and the origins of proteinuria., (Copyright © 2018 by the American Society of Nephrology.)

The kidneys in two viviparous species of Neotropical lizards, Notomabuya frenata and Aspronema dorsivittatum (Mabuyidae), were investigated by light and scanning electron microscopy in order to determine the presence of the sexual segment of the kidney (SSK) and to study its morphology. The individuals used in this study belong to the Herpetological Collection of the Herpetology Laboratory - Reptiles of the Federal University of Juiz de Fora (CHUFJF-Reptiles) and they were collected between the years 2008 and 2012 from the Cerrado region in the state of Minas Gerais, Brazil. The SSK was present only in sexually mature males (with sperm in the testes / epididymis), whereas it was absent in sexually immature males. The nephron in both species consists of renal corpuscle, proximal convoluted tubule, distal convoluted tubule, collecting duct and sexual segment of the kidney. The SSK of the analyzed species were coated with a simple columnar epithelium, with high cells, basal nucleus and in the apical portion innumerable secretory granules. This study adds to the knowledge on reproductive biology and structures related to reproductive strategies of both lizard species and viviparous Neotropical lizards.

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no existing therapeutic approach to delay or stop progression. Genetic, biochemical and pre-clinical studies have provided evidence that leucine-rich-repeat-kinase-2 (LRRK2) kinase is involved in the pathogenesis of PD, and small molecule LRRK2 inhibitors represent a novel potential therapeutic approach. However, potentially adverse target-related effects have been discovered in the lung and kidneys of LRRK2 knock-out (ko) mice and rats. It is unclear if the LRRK2 ko effect in the kidneys and lung is also induced by pharmacological inhibition of the LRRK2 kinase. Here, we show that treatment with the LRRK2 inhibitor PFE-360 in rats induces a morphological kidney phenotype resembling that of the LRRK2 ko rats, whereas no effects were observed in the lung. The PFE-360 treatment induced morphological changes characterised by darkened kidneys and progressive accumulation of hyaline droplets in the renal proximal tubular epithelium. However, no histopathological evidence of renal tubular injury or changes in the blood and urine parameters that would be indicative of kidney toxicity or impaired kidney function were observed after up to 12 weeks of treatment. Morphological changes were detected in the kidney after 2 weeks of treatment and were partially reversible within a 30 day treatment-free period. Our findings suggest that pharmacological LRRK2 inhibition may not have adverse consequences for kidney function., (Copyright © 2018 H. Lundbeck A/S. Published by Elsevier B.V. All rights reserved.)

The kidney is the most important excretory organ in the body and plays an essential role in maintaining homeostasis in vivo by conserving body fluid and electrolytes and removing metabolic waste. In this study, three types of transgenic system were used to investigate the expression of the bitter taste receptor Tas2r105 in mouse renal tissue (Tas2r105-GFP/Cre, Tas2r105-GFP/Cre-DTA and Tas2r105-GFP/Cre-LacZ). The results suggest that bitter taste receptors Tas2r105 and Tas2r106 are expressed in the renal corpuscle and the renal tubule, including the proximal tubule and distal tubule. Expression of α-gustducin, an important component of taste signal transduction, was also detected in mouse kidney. Meanwhile, conditional diphtheria toxin (DTA) expression in Tas2r105+ cells caused an increase in size of the glomerulus and renal tubule, accompanied by a decrease in cell density in the glomerulus. This indicates that Tas2r105+ cells play an important role in maintaining the structure of the glomerulus and renal tubules. Overall, the current study collectively demonstrates that cells labeled by bitter taste receptor expression may play a critical role in controlling human health, and have properties far beyond the original concept of taste perception., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report the development of a small fluorescent molecule, BDNCA3-D2, herein referred to as PT-Yellow. Soaking zebrafish embryos in PT-Yellow or intraperitoneal injection into adults results in non-toxic in vivo fluorescent labeling of the renal proximal tubules, the major site of blood filtrate reabsorption and a common target of injury in acute kidney injury. We demonstrate the applicability of this new compound as a rapid and simple readout for zebrafish kidney filtration and proximal tubule reabsorption function.

MicroRNAs (miRNAs) are major posttranscriptional regulators of a wide variety of biological processes. However, redundancy among most miRNAs has made it difficult to identify their in vivo functions. We previously demonstrated that global inhibition of miRNA biogenesis in Xenopus resulted in a dramatically smaller pronephric kidney. This suggested that microRNAs play a pivotal role in organ size control. Here we now provide a detailed mechanistic explanation for this phenotype. We identified that the activation of the mechanistic target of rapamycin complex 1 (mTORC1) by Insulin and insulin-like growth factor (Igf) 2 is an important regulator in kidney growth, which in turn is modulated by microRNAs. Molecular analyses demonstrate that microRNAs set a threshold for mTORC1 signaling by down-regulating one of its core negative regulators, tuberous sclerosis 1 (Tsc1). Most importantly, this rheostat can be reprogrammed experimentally. Whereas knockdown of miRNAs causes growth arrest, concomitant knockdown of Tsc1 restores mTORC1 activity and proximal tubular size. Together, these data establish a previously unidentified in vivo paradigm for the importance of posttranscriptional regulation in organ size control.

D-Aspartate (D-Asp) is an endogenous substance in mammals. Degradation of D-Asp is carried out only by D-aspartate oxidase (DDO). We measured DDO activity in porcine tissues, and produced an anti-porcine DDO antibody to examine the cellular localization of DDO. All the tissues examined showed DDO activities, whereas the substrate D-Asp was not detected in kidney cortex, liver, heart, and gastric mucosa. In the kidney, intensive immunohistochemical staining for DDO was found in the epithelial cells of the proximal tubules. In the liver, the epithelial cells of interlobular bile ducts, liver sinusoid-lining cells with cytoplasmic processes, and the smooth muscle cells of arterioles were strongly stained for DDO. In the heart, cardiomyocytes and the smooth muscle cells of arterioles showed DDO-immunoreactivity. In the gastric mucosa, only the chief cells were DDO-positive. These newly identified DDO-positive cells seem to actively degrade D-Asp to prevent an excess of D-Asp from exerting harmful effects on the respective functions of porcine tissues.

This study details the gross and microscopic anatomy of the pelvic kidney in male Ambystoma maculatum. The nephron of male Ambystoma maculatum is divided into six distinct regions leading sequentially away from a renal corpuscle: (1) neck segment, which communicates with the coelomic cavity via a ventrally positioned pleuroperitoneal funnel, (2) proximal tubule, (3) intermediate segment, (4) distal tubule, (5) collecting tubule, and (6) collecting duct. The proximal tubule is divided into a vacuolated proximal region and a distal lysosomic region. The basal plasma membrane is modified into intertwining microvillus lamellae. The epithelium of the distal tubule varies little along its length and is demarcated by columns of mitochondria with their long axes oriented perpendicular to the basal lamina. The distal tubule possesses highly interdigitating microvillus lamellae from the lateral membranes and pronounced foot processes of the basal membrane that are not intertwined, but perpendicular to the basal lamina. The collecting tubule is lined by an epithelium with dark and light cells. Light cells are similar to those observed in the distal tuble except with less mitochondria and microvillus lamellae of the lateral and basal plasma membrane. Dark cells possess dark euchromatic nuclei and are filled with numerous small mitochondria. The epithelium of the neck segment, pleuroperitoneal funnel, and intermediate segment is composed entirely of ciliated cells with cilia protruding from only the central portion of the apical plasma membrane. The collecting duct is lined by a highly secretory epithelium that produces numerous membrane bound granules that stain positively for neutral carbohydrates and proteins. Apically positioned ciliated cells are intercalated between secretory cells. The collecting ducts anastomose caudally and unite with the Wolffian duct via a common collecting duct. The Wolffian duct is secretory, but not to the extent of the collecting duct, synthesizes neutral carbohydrates and proteins, and is also lined by apical ciliated cells intercalated between secretory cells. Although functional aspects associated with the morphological variation along the length of the proximal portions of the nephron have been investigated, the role of a highly secretory collecting duct has not. Historical data that implicated secretory activity concordant with mating activity, and similarity of structure and chemistry to sexual segments of the kidneys in other vertebrates, lead us to believe that the collecting duct functions as a secondary sexual organ in Ambystoma maculatum., (© 2010 Wiley-Liss, Inc.)

The three-dimensional architecture of nephrons in situ and their interrelationship with other nephrons are difficult to visualize by microscopic methods. The present study uses microcomputed X-ray tomography (micro-CT) to visualize intact nephrons in situ. Rat kidneys were perfusion-fixed with buffered formalin and their vasculature was subsequently perfused with radiopaque silicone. Cortical tissue was stained en bloc with osmium tetroxide, embedded in plastic, scanned, and reconstructed at voxel resolutions of 6, 2, and 1 microm. At 6 microm resolution, large blood vessels and glomeruli could be visualized but nephrons and their lumens were small and difficult to visualize. Optimal images were obtained using a synchrotron radiation source at 2 microm resolution where nephron components could be identified, correlated with histological sections, and traced. Proximal tubules had large diameters and opaque walls, whereas distal tubules, connecting tubules, and collecting ducts had smaller diameters and less opaque walls. Blood vessels could be distinguished from nephrons by the luminal presence of radiopaque silicone. Proximal tubules were three times longer than distal tubules. Proximal and distal tubules were tightly coiled in the outer cortex but were loosely coiled in the middle and inner cortex. The connecting tubules had the narrowest diameters of the tubules and converged to form arcades that paralleled the radial vessels as they extended to the outer cortex. These results illustrate a potential use of micro-CT to obtain three-dimensional information about nephron architecture and nephron interrelationships, which could be useful in evaluating experimental tubular hypertrophy, atrophy, and necrosis.

Aim: The renal tubular uptake of 125I-Aprotinin (*Ap) is on average located more superficially than its filtration site, causing transfer of some of *Ap filtered in deep to more superficial cortical zones. 125I-Cystatin C (*Cy) showed less uptake in deep cortical zones than Ap, suggesting a longer and/or a more superficial tubular uptake site. To test that hypothesis and to quantify the outward transfer of the filtered polypeptides, we estimated the tubular uptake pattern of the tracers in perfusion fixed rat kidneys after intravenous injection of *Cy and *Ap., Methods: Autoradiographs were made from 10 mum thick slices of Microfil nephron casts from outer (OC), middle (MC) and inner (IC) cortical zones to quantify cortical border-crossing *Ap transfer. Single nephron glomerular filtration rate (snGFR) was estimated as the zonal uptake of *Ap corrected for *Ap transfer, divided by its time-integrated plasma concentration and the zonal number of glomeruli., Results: *Ap and *Cy uptake fell exponentially along the proximal convoluted tubule (PCT), indicating an uptake proportional to luminal concentration. Uptake in IC exceeded that in MC and OC nephrons. The per cent PCT length with *Cy uptake (67.2 +/- 1.6) exceeded that of *Ap (54.6 +/- 1.8). The zonal border-crossing PCT length (29-34% of total PCT) from deep to more superficial cortical zones transferred 4-6% more *Cy than *Ap., Conclusion: Greater tubular uptake length of *Cy than of *Ap causes more cortical border-crossing of *Cy. The zonal snGFR estimated from Aprotinin uptake corrected for border-crossing agreed well with that obtained with the Hanssen ferrocyanide technique.

Background: Proximal tubule (PT) angiotensinogen (AGT) is part of a tubular renin-angiotensin system (RAS) that participates in the regulation of sodium reabsorption along the entire nephron. Physiologic maneuvers affecting AGT expression in PT also affect systemic RAS. Here, we tested the hypothesis that PT AGT is regulated by increased glomerular filtration rate (GFR)., Methods: Complete unilateral nephrectomy (UNX) in mice was used to induce a sustained increase in GFR in the remaining kidney. AGT expression was monitored by quantitative reverse transcription-polymerase chain reaction (RT-PCR). AGT protein in PT was investigated by semiquantitative histology. We also measured AGT concentration in plasma and in 24-hour urine by a specific enzyme-linked immunosorbent assay (ELISA)., Results: Seven weeks after nephrectomy, UNX animals exhibited a 2-fold increase in tubular AGT mRNA (P <.001) compared with sham-operated control animals. The proportion of PT sections exhibiting AGT immunostaining was significantly increased at day 3 (P <.05), and remained elevated at seven weeks (UNX = 0.63 +/- 0.09, sham = 0.38 +/- 0.02, P <.01), revealing recruitment of AGT-producing cells along the PT. AGT excretion in final urine corrected for creatinine and kidney weight was also elevated by UNX at seven weeks (UNX = 209 +/- 42 pmol/mg/g, sham = 147 +/- 29 pmol/mg/g, P <.05), with no difference in plasma AGT between UNX and control animals., Conclusion: These observations suggest that AGT expression in PT adapts in the long-term to changes in GFR. In the UNX model, urinary AGT excretion is also elevated as a consequence of increase in net tubular flow.

The DBA/2Cr mouse is characterized by the presence of giant lysosomes located in the proximal convoluted tubules of males and proximal straight tubules of females. However, it remains unclear whether these giant lysosomes in the proximal tubules are characteristic of DBA/2Cr specifically, or are common to other DBA/2 substrains and DBA/1. The present study investigated the morphology of kidneys from DBA/2CrSlc, DBA/2JJcl, DBA/2NCrj and DBA/1JNCrj mice of both sexes. Giant lysosomes in the renal proximal tubules were found to represent common morphological characteristic of both DBA/2 and DBA/1JN.

The review presents a modern view on the functional--morphological peculiarities of 12 segments of the nephron canaliculi possessing some functional, biochemical and histologic distinctions that should be taken into account to study physiology, biochemistry, morphology and pathophysiology of the kidney.

In the present study, we performed comparative histological observations of ICR, BALB/c, C57BL/6, C3H/HeN and DBA/2 mice kidneys. Sex and strain differences were observed in the appearance of vacuolar structures of the proximal convoluted tubules (toluidine blue-positive granules in osmium-postfixed epoxy-resin sections). These features were especially remarkable in male DBA/2 mice. The vacuolar structures in male DBA/2 mice showed heterogeneous staining with Sudan B in frozen sections and appeared under an electron microscope as multilammelar giant dense bodies. In addition, these dense bodies showed heterogeneous acid phosphatase reactions. Immunohistochemical analyses of these structures for apolipoprotein B showed strong positive reactions. These results suggested that vacuolar structures in the proximal convoluted tubules, which were remarkable in male DBA/2 mice, were giant lysosomes containing apolipoprotein B.

We developed a model of volume contraction in rabbits by using a furosemide/low-salt diet to follow changes, if any, in proximal tubule Na+/H+ exchanger 3 (NHE3) mRNA and brush-border protein. The rabbits' plasma renin, aldosterone, and urine sodium content confirmed the volume-contracted state. RNase protection assays demonstrated increases in treated-animal NHE3 mRNA as a percentage of control with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 +/- 7 (SE) % (P < 0.05) at 1, 5, 10, and 31 days, respectively. Western analysis of brush-border membrane with NHE3 antibody revealed increased immunoreactivity in treated animals as a percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P < 0.05) at 1, 5, 10, and 31 days, respectively. There was no significant difference in serum potassium, bicarbonate, and cortisol in control vs. experimental animals. These data suggest that there is chronic upregulation of NHE3 in the volume-contracted state.

Seasonal variability in kidney morphology of the house sparrow Passer domesticus was examined using light microscopy. Sparrows were captured from the wild in winter, spring, summer and autumn. The kidneys were perfused with half-strength Karnovsky's fixative and processed for light microscopy by embedding in either paraffin wax or JB4 acrylic resin. Absolute volumes of the kidneys, their components (cortex, medulla and blood vessels), components of the nephron (renal corpuscles, proximal tubules, loops of Henle, distal tubules and collecting ducts) and the capillaries surrounding the nephron were quantified using stereology. Tissue processed in paraffin wax had a mean shrinkage of 17.7 % compared with 10.1 % in JB4 resin. Absolute volumes of the kidneys and nephrons were compared statistically between tissue processing methods and among seasons. Absolute volumes of the structures within the kidneys were not significantly different between treatments or among seasons. Within the nephron, the only measured variables to show significant differences were the absolute volumes of the distal tubules and cortical collecting ducts between tissue processing treatments. Thus, kidney morphology was relatively unaffected by changes in season. In addition, the results show that embedding tissue using acrylic resin causes less shrinkage, and it should therefore be the preferred embedding medium for quantitative morphologists.

The organization of the renal medulla of the Gambel's quail, Callipepla gambelii, kidney was examined to determine the number of loops of Henle and collecting ducts and the surface area occupied by the different nephron segments as a function of distance down the medullary cones. Eleven medullary cones were dissected from the kidneys of four birds, and the tissue was processed and sectioned for light microscopy. In addition, individual nephrons were isolated on which total loop thin descending segment and thick prebend segment lengths were measured. The results show no correlation between the absolute number of loops of Henle and the length of the medullary cones. The number of thick and thin limbs of Henle and collecting ducts decrease exponentially with distance toward the apex of the cones and the rate of decrease is similar for cones of different lengths. Initially there is a rapid decrease in the number of thin limbs of Henle, indicating that most nephrons do not penetrate the cones a great distance. Thick descending limbs of Henle (prebend segment) ranged in length from 50 to 770 microm, and there was little correlation with the total length of the loop of Henle. However, the length of the thin limb of Henle correlated well with total loop length. The cell surface areas of the limbs of the loop of Henle and the collecting ducts decreased toward the apex of the cones.

Glutamine synthesis, a major process for ammonia detoxification and the control of acid-base balance, occurs from various precursors in suspensions of rabbit proximal tubules. However, no data are currently available on the distribution of glutamine synthesis along the rabbit proximal tubule, and its modulation by changes of substrate concentration. Therefore we have microdissected and incubated the three parts (S1, S2 and S3) of rabbit proximal tubules and measured glutamine synthesis from alanine and aspartate. With a physiological concentration of alanine (0.25 mM) or aspartate (0.05 mM), glutamine synthesis in the S1 segment was about half of that in the S2 and S3 segments, and was greater from alanine than from aspartate along the entire proximal tubule. Elevation of alanine and aspartate concentrations to 5 mM increased glutamine synthesis in both a substrate- and segment-dependent manner. It is concluded that glutamine synthesis occurs from alanine and aspartate along the entire rabbit proximal tubule; however, contrary to what might have been expected on the basis of measurement of glutamine synthetase activity, the basal rate of glutamine synthesis and its adaptation to increased substrate availability are heterogeneous along this nephron segment.

Diabetes in now the commonest cause of renal failure in the western world. Furthermore the survival of diabetic patients requiring dialysis treatment for renal failure is far less than patients with renal failure secondary to all other diseases. It is therefore important to identify the factors that control the development of progressive renal disease to allow targeted therapeutic interventions which would have major implications both to patient well-being and also to the provision of health care world wide. In this review we discuss possible metabolic consequences of hyperglycemia and their role in the pathogenesis of diabetic nephropathy. We also focus on the involvement of the pro-fibrotic cytokine Transforming Growth Factor beta, and contrast its role in the pathogenesis of glomerular and tubulo-interstitial changes seen in diabetic nephropathy.

Effects of maternal uninephrectomy in rats, which was performed on day 5 of gestation, on development of proximal renal tubule of the pups were morphometrically investigated. One day after birth, both the proximal tubular length per unit volume (1 mm3) of whole kidney and total proximal tubular volume in the neonates from uninephrectomized mothers were significantly larger than those in the neonates from sham-operated mothers. Six weeks after birth, no significant differences in parameters of the kidney were observed between the pups from uninephrectomized and sham-operated mothers. These results suggest that maternal uninephrectomy in the rat accelerates the development of proximal renal tubule in the fetus and that the renotropic activity is not lasting during postnatal development of the kidney.

The subcellular distribution and segmental variations in location of gp330, a scavenger receptor for filtered proteins in renal proximal tubules, was analyzed. Kidney tissue from rats (4 different strains), rabbits and humans were analyzed by light- and electron microscope immunocytochemistry, using cryosections or Lowicryl sections from cryosubstituted tissue. Gp330 was located mainly in apical coated pits, small and large endocytic vacuoles and in dense apical tubules in the proximal tubule cells. The labeling density was markedly higher in segments 1 and 2 as compared to segment 3 of the proximal tubule. In addition to the location in the early part of the endocytic pathway, gp330 was also present in lysosomes, especially in segments 1 and 2. The lysosomal labeling was not restricted to the membrane, but was also seen in the matrix. Localization of gp330 in lysosomes was confirmed on sections from purified lysosomal fractions from rat renal cortex. The brush border localization of gp330 in proximal tubules exhibited a characteristic segmental variation. In the initial part of segment 1, there was virtually no brush border labeling. In the remaining part of segment 1 and in segment 2, there was a distinct but sometimes patchy labeling of the brush border. In segment 3, groups of microvilli of approximately 10 as seen in sections were intensively labeled from bottom to tip and there were often more than one of these groups on a single cell, the remaining microvilli were unlabeled. No differences in the cellular and subcellular localization of gp330 were observed between species or rat strains. In conclusion, the present study demonstrates that in addition to its location in the early endocytic and recycling pathway, gp330 is also present in microvilli and the protein and degradation products thereof is present in lysosomes, consistent with its role as a protein scavenger receptor.

Previous research in animals and humans has demonstrated that many nephrotoxic chemicals induce selective injury within the kidney affecting either renal proximal straight (PST) or proximal convoluted (PCT) tubules. Selective injury has also been observed following in vitro nephrotoxicant exposure to precision-cut renal slices and isolated PCT and PST segments. These in vitro models provide a means of comparing and contrasting basic mechanistic differences which render these segments innately susceptible to nephrotoxicant injury. In this article, methods for preparing precision-cut slices and isolating PST and PCT segments will be reviewed.

Oligonucleotide probes were designed to sequences of the rat alpha 1B- and alpha 2B-adrenergic receptor mRNA and used for in situ hybridization histochemistry on tissue sections of kidneys from control and thyroidectomized rats. Both alpha 1B- and alpha 2B-receptor mRNA labelling was demonstrated in proximal tubule cells in the outer stripe of the outer medulla, with tubular rays radiating into the cortex. Thyroidectomy induced a more than 4-fold increase in mRNA for the alpha 1B-receptor in the kidney, whereas no change in alpha 2B-receptor mRNA levels could be demonstrated in thyroidectomized rats as compared to control animals. The results suggest that thyroid hormone plays an important role in regulating expression of alpha 1B-receptors in renal tubule cells.

The ultrastructure of renal tubule cells was studied in the European lesser spotted dogfish by the evaluation of thin sections and freeze fracture replicas. Computer-assisted three-dimensional reconstruction of entire nephrons was performed. The distinction of nephron segments and collecting tubule was made using results of previous histological work. The first proximal tubule segment (PI) consists of two subsequent portions, PIa and PIb. PIa is a component of the lateral countercurrent bundle, and PIb, which displays an apical tubulovesicular apparatus and an extended lysosomal compartment, is located in the vicinity of the glomeruli. Rod-shaped intramembrane particles were detected in PIa. The second proximal tubule segment (PII) is a special segment in elasmobranch and teleost fish. PII differs largely from PI in cell morphology and function. The apical cytoplasm was filled with small clear vesicles, and an apical endocytic apparatus was lacking. In the apical cell membrane, rod-shaped particles were revealed by freeze fracture. The apical tight junctions of PI and PII consisted of seven to ten meandering strands. The distal nephron was subdivided into two major segments: early distal tubule (EDT) in the lateral countercurrent bundles and late distal tubule (LDT) in the mesial tissue. The EDT showed marked amplification of basolateral cell membranes. The tight junctions displayed a low number of continuous parallel strands, which is also characteristically found in the diluting segments of other vertebrates. LDT cells showed cytoplasmic studs and rod-shaped intramembraneous particles at the apical cell membrane, thereby resembling type A intercalated cells of collecting duct. The collecting tubule (CT) emerged from the LDT and was part of the countercurrent arrangement inside the lateral bundles. Tight junctions of LDT and CT consisted of many meandering strands in a honeycomb pattern. With immunohistochemistry, binding sites of a polyclonal antibody against an extraplasmic portion of rat gastric H(+)-K(+)-adenosine triphosphatase (ATPase) were observed at the apical cell membrane of PIa, PII, and LDT. From the colocalization of binding sites for the antibody against the transport enzyme with rod-shaped intramembrane particles, we assume that these might be the morphological correlate of gastric H(+)-K(+)-ATPase-like enzyme in the renal tubule.

The platypus kidney shows morphological similarities to those of other mammals. Macroscopically, the cortex is easily distinguishable from the fairly wide medulla. Within the medulla, no clear border is observed between the inner and outer zones. Light and transmission electron microscopically, the glomeruli show quite similar architecture to those of other mammals; however, the glomerular lobulation is very clear. The glomerular tufts are rather simple, but capillary lumen varies widely in size, which is one of the unique features of the platypus kidney. The urinary tubule is generally similar to that of human and other mammals in shape and segmentation; however, the staining specificities of histochemical reactions and the shape of epithelial cells of the Henle's loop differ from those of other mammals. The most conspicuous features are: 1) although no protein casts are found in the tubular lumina, epithelial cells of the proximal convoluted tubule (PCT) have numerous electron-dense vesicles as in human nephrotic kidneys; and 2) the platypus Henle's loop consists of the thick epithelial cells similar to the mammalian type nephron of birds. As compared to those of other mammals such as humans and rats, our observations suggest that the platypus kidney is less developed, in terms of evolution.

120 male rats belonging to two different strains (Han: WIST, Han: SPRD) and two different weight groups (group I: lighter body weight, group II heavier body weight) were killed on three different methods (decapitation, Nembutal -overdose greater than 250 mg/kg b.w. i.p. less than, exsanguination in Nembutal -anaesthesia greater than 100 mg/kg b.w. i.p.). Subsequently, changes in tubuli contorti I of the left kidneys were examined morphometrically. The mean total area, luminal area and epithelial area were evaluated as well as the mean diameter of the tubular nuclei. Concerning the areas of the proximal tubules only the luminal areas show differences between the Wistar and the Sprague-Dawley strain. The total, luminal and epithelial area in the rats belonging to the weight group II were significantly larger than in the rats belonging to weight group I. With one exception this could be noticed within both strains and all three modes of killing. In both strains and weight groups the rats were killed by Nembutal -overdose or exsanguination showed significantly smaller total, luminal and epithelial areas than the rats that were decapitated. Possible cause heretofore are discussed. Differences between the tubular areas of the rats that were killed by Nembutal -overdose and those that were killed by exsanguination after Nembutal -anaesthesia could not be established. The measurements of nuclei diameters in the proximal tubules did not lead to clearly different results between both strains, weight groups and the various modes of killing.

Using the cheek pouch of the Syrian hamster as an experimental model for oral carcinogenesis, it has been shown that the expression of transforming growth factor-alpha (TGF-alpha) is consistently associated with the malignant transformation process. We have recently shown that production of TGF-alpha has been localized to normal hamster oral epithelium and bone marrow eosinophils. In this study we investigated the production of this cytokine in other normal hamster adult tissues. By using an EGF-radioreceptor assay, immunohistochemistry, Northern blot analysis, and in situ hybridization we have now further detected the presence of TGF-alpha mRNA and/or protein in the kidney, stomach, and pancreas of normal adult hamster. Together with the previously reported detection of TGF-alpha in oral mucosa and bone marrow eosinophils, these adult normal tissue/cellular sources can serve as sites of TGF-alpha production. The availability of hamster specific reagents (cDNA and monoclonal antibodies) and the delineation of the various adult tissues that could produce TGF-alpha make the Syrian hamster a suitable model for the study of how this multifunctional cytokine can influence normal and pathological processes.

In dual micropuncture experiments the shrinking drop technique was used to measure volume flux with artificial tubular fluid (AF) alternating with harvested tubular fluid (HTF) during saline volume-expanded (VE) and nonexpanded (NE) periods. In VE rats, volume flux (Jv) (nl.mm-1.min-1) with AF was 1.78 +/- 0.08 (means +/- SE) during NE and was reduced to 1.39 +/- 0.09 (P = 0.01) during subsequent VE, whereas with randomly alternating HTF during VE it was 1.07 +/- 0.08 (P less than 0.0001 and less than 0.03, respectively). Jv with HTF from NE rats tested in the VE rats was 1.20 +/- 0.06, which is significantly higher than that measured with their own HTF (Wilcoxon rank, P = 0.05). In NE rats Jv was 1.65 +/- 0.10 and 1.69 +/- 0.10 with AF and HTF and was 1.28 +/- 0.07 (P less than 0.001 from both) with HTF obtained from VE rats. Elemental analysis of reaspirated tubular fluids showed no significant differences in Na or Cl concentrations among any of the fluids. It is concluded that during VE, a transferable Na transport inhibitor appears in proximal tubular fluid, which, together with a changed proximal tubular epithelium, possibly due to physical forces, accounts for proximal tubular Na transport inhibition during VE.

The structure of the nephron in the ranid frog, Rana cancrivora, was studied by light and electron microscopy. This frog is the only amphibian species to live in mangrove swamps of very high salinity. The nephron consists of the following parts: renal corpuscle, ciliated neck segment, proximal tubule, ciliated intermediate segment, distal tubule, connecting tubule, and collecting duct. The distal tubule is located in the ventromedial region of the kidney, and the other tubules are situated in the dorsolateral region. Renal corpuscles are found between the two regions. Some renal corpuscles have a wide Bowman's space because of the small glomerulus within them. The proximal tubules are composed of columnar cells with a dense luminal brush border of long microvilli and numerous apical vesicles and vacuoles. The initial part of the distal tubule consists of heavily interdigitated cells, characterized by a very regular palisade arrangement of mitochondria. In the terminal part of the distal tubule, shorter mitochondria of the infolding cells are situated irregularly around the nucleus. The connecting tubule consists of principal cells and canaliculus cells. The collecting duct consists of columnar or cuboidal cells; cytoplasmic organelles are relatively sparse. The canaliculus cells are intercalated between principal cells from the terminal distal tubule to the proximal part of the collecting duct. Our findings indicate that the kidney of R. cancrivora is structurally similar to kidneys of other amphibians. These findings are discussed with regard to probable correlations between ultrastructure and function in R. cancrivora.

To measure simultaneously the concentration profiles of bicarbonate, chloride and inulin along the length of the superficial proximal convoluted tubule, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Bicarbonate and volume reabsorption were 354 +/- 21 pmol X mm-1 X min-1 and 5.9 +/- 0.4 nl X mm-1 X min-1 in the first millimeter and fell progressively in the remaining 3.8 mm of tubule, averaging 83 +/- 4 pmol X mm-1 X min-1 and 2.3 +/- 0.5 nl X mm-1 X min-1, respectively. The values in the initial millimeter represents a high transport capacity since they exceed rates that have been observed when comparable or even higher mean luminal substrate concentrations were presented to the late proximal tubule. In contrast, chloride reabsorption was only 206 +/- 55 peq X mm-1 X min-1 in the first millimeter compared with a mean of 306 +/- 22 peq X mm-1 X min-1 in the rest of the tubule. In conclusion, there is substantial axial transport heterogeneity, with bicarbonate and water reabsorption higher but chloride reabsorption lower in the early compared with the late superficial proximal convoluted tubule.

Conflicting data exist regarding the ability of the rat proximal convoluted tubule to maintain a transepithelial gradient for CO2 and the effects of carbonic anhydrase on CO2 permeability. The present in vivo microperfusion experiments were designed to assess the ability of the rat proximal tubule to sustain a CO2 gradient between tubule lumen and peritubular blood. Tubules were perfused at rates ranging from 10 to 100 nl/min with isotonic sodium chloride containing no CO2. Peritubular capillary and intraluminal PCO2 was measured during microperfusion with PCO2 microelectrodes to allow determination of the transepithelial CO2 gradient. The mean PCO2 measured in peritubular capillaries of control rats was 60.6 +/- 1.9 mmHg. Since the perfusion solution initially contained no CO2, a gradient of 60 mmHg was imposed across the tubule epithelium. Intraluminal PCO2 rapidly approached that of the surrounding capillaries. At a tubule perfusion rate of 20 nl/min, the gradient between lumen and blood decreased to 0.9 mmHg, a value not significantly greater than zero. The calculated CO2 permeability coefficient (KCO2) was 3.69 X 10(-5) cm2/s. Addition of either 10(-4) M acetazolamide or benzolamide did not prolong the rapid dissipation of the imposed CO2 gradient. The KCO2 during carbonic anhydrase inhibition was not significantly different from control values. It is concluded that the rat proximal tubule does not present a physiologically significant diffusion barrier to CO2 either in the presence or absence of carbonic anhydrase activity. The previously demonstrated acid disequilibrium pH in the proximal tubule during inhibition of carbonic anhydrase represents an intraluminal accumulation of carbonic acid rather than of carbon dioxide gas.

Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.

The microscopic structure of the various nephron segments comprising the medullary counterflow system is described. The architectural organization of the tubules and blood vessels in the inner and outer medulla is also described. Species differences are noted. A hypothesis that the thicker parts of the descending limbs of Henle actively secrete salt is advanced.

A new method to measure time dependent (t) volume (V) changes in proximal straight tubules (PST) is described. V is calculated from diameter (d) measurements for which a video camera and an integrating circuit are used. A tubular image of high optical contrast is recorded with the TV camera such that the scan lines run crosswise to the tubule. The video signal is analyzed by a special processor which adds 225 tubular diameters of each TV frame and feeds this analog signal to a pen recorder. The fractional error in d measurements is 10(-3). Diameter changes of less than 0.05 micron can be detected, as compared to the usual error of a single measurement of about 0.4 micron. Pcbos, the osmotic water permeability of the contraluminal cell membrane was measured by setting up osmotic steps across it in less than 0.1 s and following the ensuing delta d/delta t. The time delay between solution change and the linear part of the osmotic response was 0.51 +/- 0.05 s. Pcbos was found to be 50.4 (+/- 8.7) X 10(-4) cm3.cm-2 of basement membrane area .s-1.osmolar-1.

Rabbit proximal straight tubules rapidly swell to a maximum volume when abruptly immersed into hypotonic medium. However, in a second, slower phase, termed volume regulatory decrease (VRD), tubules shrink toward their basal volume due to the efflux of K, accompanying anion and water. In the present study, we investigated the nature of the anion during hypotonic volume regulation. We removed Cl and/or the HCO3 buffer to assess their relative importance in VRD, and we used furosemide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), and barium to investigate the nature of the transmembrane anion pathway in VRD. Isosmotic replacement of peritubular Cl with gluconate had no effect on either tubule volume in isotonic medium or the initial osmometric swelling response in hypotonic medium. However, the VRD in such Cl-depleted tubules was significantly inhibited. Control tubules regulated 81% below their maximal volume in dilute medium. By contrast, Cl-depleted tubules regulated only 39%. This inhibitory effect could not be attributed to the absence of peritubular Cl or to the presence of gluconate. The absence of the HCO3 buffer or the presence of SITS (0.5 mM) had no inhibitory effect on the rate or extent of VRD. Furosemide alone (1 mM) also had no inhibitory effect on VRD. However, whereas barium alone delays VRD, addition of furosemide to barium-treated tubules further slowed their maximal rate of fluid efflux and delayed VRD even more.(ABSTRACT TRUNCATED AT 250 WORDS)

Inosine 5'-diphosphatase (IDPase) activity was demonstrated cytochemically in the endoplasmic reticulum of rat kidney proximal tubule cells in tissue fixed by perfusion with glutaraldehyde--formaldehyde. Incubation for IDPase activity at pH 7.2 was performed with and without 0.5 mM levamisole, a potent inhibitor of alkaline phosphatase (AlkPase) (M Borgers, J Histochem Cytochem 21:812, 1973). Levamisole treatment of sections eliminated all reaction product in the brush border, but did not affect the IDPase activity the endoplasmic reticulum (ER). The ER appears as a basilar-luminal-oriented transcellular structure, suggesting a possible cellular transport route. This study supports and extends earlier observations made by others that suggest a transport role for the ER in these cells. It also emphasizes the value of thick section cytochemistry.

This review contrasts the glucose transport mechanisms at opposing surfaces of the renal proximal convoluted tubule: the Na+-dependent D-glucose transporter localized at the brush border membrane and the Na+-independent transporter localized at the basolateral surface. The two sugar transport mechanisms are discussed from the point of view of their specificity, kinetic, and regulatory behaviors. Recent results focussing on molecular characterization of these different carrier proteins are also described, including some newer information on purification of the Na+-dependent glucose carrier from the brush border membrane.

New nephron anlages appear in the renal cortex up to the 4th postnatal day (PD). The last anlages to be formed develop into functional nephrons by PD 10, and the cortex appears mature at PD 12 after formation of the cortex corticis. The renal medulla develops by the longitudinal growth of loops of Henle and collecting ducts. The immature medulla cannot be divided into different zones and corresponds structurally to the later inner stripe of the outer zone. The inner zone is formed by PD 8, and the outer stripe of the outer zone by PD 12. The renal medulla is mature at PD 21. From the start of its development, the renal proximal tubule consists of the pars convoluta and pars recta. In both parts the formation of the brush border is accompanied by the simultaneous appearance of brush border enzymes (alkaline phosphatase, gamma-glutamyltranspeptidase, dipeptidylaminopeptidase IV) and lysosomal enzymes (acid phosphatase, acid beta-galactosidase, N-acetylglucosaminidase, dipeptidylaminopeptidase II) over the full length of the proximal tubule. During the course of proximal tubule maturation, however, the lysosomal enzyme activities decline in the pass convoluta (with constant brush border enzyme activities), while the brush border enzyme activities increase in the pars recta (with constant lysosomal enzyme activities). The two parts further differ in that they exhibit different lysosomal patterns from the outset, the pars convoluta containing numerous large, highly enzyme-active lysosomes arranged in groups, and the pars recta containing only a few very small lysosomes with low enzyme activity. Thus, even in the newborn rat, the lysosomal pattern of the pars recta already corresponds to that of the mature S3 segment. The S1 and S2 segments of the pars convoluta first differentiate between PD 10 and 21, as the groups of large lysosomes are progressively broken up and the extent of the lysosomal apparatus is diminished, this proceeding in a retrograde direction from the end of the immature pars convoluta.

Tubular organization and vascular-tubular relations were studied by double injection in canine kidneys. Blood vessels were injected via the artery after perfusion fixation. Tubules were injected by micropipettes inserted into the urinary spaces of selected glomeruli in cleared slices. One hundred proximal convoluted tubules, 16 Henle loops, and 5 distal convoluted tubules were defined. Only subcapsular proximal convolutions were perfused by efferent vessels arising from the same glomerulus (43 of 55). In midcortex, proximal convolutions were generally perfused over less than half their length by the parent efferent (21 of 31). Here tubules entirely perfused by the parent efferent were rare (2 of 31). No inner cortical proximal convolutions were perfused by the efferent from the same glomerulus (0 of 14). Henle's loops were found to be perfused by the efferents of many glomeruli regardless of the cortical position of the parent glomerulus. Distal convolutions shared the perfusion of proximal convolutions of the same glomerulus. Thus, each nephron is apparently functionally dependent on efferent blood from glomeruli of many other nephrons. New synoptic diagrams of canine renal organization are presented.

Mesonephric kidneys of the mid-gestation fetus and metanephric kidneys of the adult are known to differ in many gross features but to be qualitatively similar in their cellular morphology. In the present studies, quantitative morphometric and in vitro microperfusion procedures were used to examine further the physical and transport properties of mesonephric and metanephric (S2) proximal tubule segments from rabbit. In perfused mesonephric proximal tubules the volume transport rate was 0.91 +/- 0.08 nl/min per mm tubule length, 2.7 +/- 0.2 nl/min per mm2 basement membrane (outer tubule) surface area, and 0.19 +/- 0.03 nl/min per mm2 basolateral cell membrane surface areas. For comparison, the S2 portion of metanephric proximal tubules is reported to transport 0.33 +/- 0.02 to 0.53 +/- 0.01 nl/min per mm length or, based on the present findings, 2.8 +/- 0.2 to 4.4 +/- 0.8 nl/min per mm2 basement membrane area and 0.16 +/- 0.02 to 0.25 +/- 0.07 nl/min per mm2 basolateral membrane area. Thus, proximal mesonephric and S2 metanephric segments exhibit approximately the same transport per unit area of basement membrane and per unit area of the basolateral cell membranes across which active transport presumably occurs.

The kidneys from 6 domestic fowl were fixed in situ by perfusion from the left ventricle. In the bird there are two types of nephrons. One reptilian-type without Henle's loop and medullary tissue, and one mammalian-type with Henle's loop lying in medullary tissue. Serial sections from kidney tissue embedded in plexiglass or in paraffin were used to study the architecture of eight reconstructed reptilian-type nephrons from different cortical levels. All reconstructed nephrons had four major bends, but particularly in the subcapsular nephrons additional bends parallel to the kidney surface were found. There was no loop of Henle, but before entering the collecting duct the distal tubule usually had a very thin-walled segment. No proximal convoluted part was found in the reptilian-type nephrons. The length of the tubules varied between 3,000 microns and 6,000 microns. In the distal tubule a macula densa segment was found in all nephrons of the reptilian and mammalian type. The capillary network between the inter- and intralobular veins was composed of increasingly larger capillaries towards the intralobular vein. Segments of the distal tubule were indented into these capillaries and completely surrounded by them. In the nephrons of the mammalian type the proximal tubule was found to be convoluted as is usual for mammalian species.

Morphologic and physiologic studies have established that filtered proteins are absorbed in the proximal tubule by endocytosis and transported to the lysosomes for degradation. The tubular absorption, hydrolysis and accumulation of albumin were examined in all three segments of the rabbit proximal tubule. S1, S2 and S3 segments were dissected and perfused in vitro with tritiated albumin at a physiologic concentration of 0.0364 mg/ml, and with [14C]inulin to determine fluid reabsorption. In addition, the three segments were fixed for ultrastructural examination after perfusion under conditions similar to those in the physiologic studies. The fluid reabsorption was similar in S1 and S2 but lower in S3. Albumin absorption was unexpectedly similar in the three segments. A lower percentage of absorbed albumin was hydrolyzed in the S3 segment compared with the earlier segments. The values were 70 +/- 15%, 61 +/- 11%, and 30 +/- 4% for S1, S2, and S3, respectively. The cellular accumulation of protein was highest in the S3 segment. The ultrastructure of the three segments was similar to that described in in vivo preserved kidneys, and no abnormalities were observed in the endocytic-lysosomal compartment. These results reveal axial heterogeneity in the hydrolysis of absorbed albumin by the rabbit proximal tubule and suggest that under normal physiologic conditions the S3 segment has a lower lysosomal proteolytic activity. Although the S3 segment maintains a high capacity for protein absorption, the earlier proximal segments likely have a greater role in protein degradation.

Silicone rubber injections of methyl salicylate-cleared rat kidneys were performed. In 50 of 56 injections of superficial nephrons with their accompanying blood supply, the efferent vessel and early proximal tubule were closely approximated. In 18 of 21 tubular injections filling through the pars recta, the proximal tubule folded upon itself with early and late proximal segments, in close contact, located over their parent glomerulus, and the midproximal segments separate and located over their parent interlobular artery. The distribution of blood was serially through the early-late proximal region above the glomerulus via a long unbranched efferent vessel, via branches over the capsular surface, via capillaries down through the midproximal region, then into the interlobular vein. The observed anatomical pattern of the superficial nephron appears to permit direct functional interactions between the juxtaposed early and late proximal tubule, and in turn may effect midproximal function via the distribution of blood (modified by early proximal) from the efferent vessel to midproximal convolutions. In addition, the relationship between specific segments of the proximal tubule and specific portions of the postglomerular peritubular blood supply may be important in determining the distribution of peritubular physical forces to these nephrons.

The single nephron glomerular filtration rate (SNGFR) was determined in superficial (S) and juxtamedullary (JM) nephrons of 10 anesthetized rabbits by the 14C ferrocyanide infusion technique. The length of the proximal tubules and the volume of the glomeruli were also determined for the same nephrons. SNGFR was higher in JM than in S: 28.6 +/- 3.4 versus 22.6 +/- 3.0 nl/min, P less than 0.001. In JM nephrons, glomeruli were larger than in S: 1.3 +/- 0.1 versus 0.9 +/- 0.1 nl, P less than 0.001, whereas there was no difference between proximal tubule length in either category (s, 8.7 +/- 0.3 and JM, 8.9 +/- 0.5 mm). In 6 out of 8 animals, SNGFR was significantly correlated to glomerular volume. Lack of correlation was observed between SNGFR and length of proximal tubule in all animals but one. These results show that the rabbit, as well as small rodents and the dog, has a higher SNGFR in juxtamedullary than superficial glomeruli. Although this functional difference is not related to the length of the proximal tubule in each individual animal, the ratio between the mean SNGFR value and the mean length of the proximal tubule in superficial rabbit nephrons is similar to the ratio found in other species.