Morphogenesis of the renal juxtaglomerular apparatus and peripolar cells in the sheep

Summary The morphogenesis of the juxtaglomerular apparatus and peripolar cells was studied in the metanephros of fetal sheep (from 24 to 147 days of gestation) using light and electron microscopy. The first juxtaglomerular apparatus was detected at 45 days of gestation, following constriction of the edges of Bowman's capsule and formation of the vascular pole of the renal corpuscle. Mesenchymal cells gave rise to lacis cells and to smooth muscle and epithelioid cells of the juxtaglomerular arterioles. Epithelioid cells developed only sparse cytoplasmic granulation, first detectable at 92 days. The macula densa developed from tubular cells at the junction of the middle and upper limbs of the S-shaped body of the developing nephron. Peripolar cells arose from epithelial cells in the lower limb of the S-shaped body, at the constricting edges of Bowman's capsule, and formed a cuff around the origin of the glomerular tuft. Cytoplasmic granules were first detected in peripolar cells at 53 days, and remained more prominent than epithelioid cell granulation throughout gestation.     

Renal microvasculature of the black bear (Ursus americanus)

This study of the Black bear (Ursus americanus) was undertaken to provide basic information related to structural modifications in the renal microvasculature that might provide insight into the drastic alteration in renal urinary output that occurs during winter sleep. Vascular casts, as well as light microscopy and scanning electron microscopy, were used to study the vascular components of the juxtaglomerular complex and related vessels. Histologically, arterial cushions were readily identified at the origin of the afferent arterioles. In the area of the juxtaglomerular complex, the wall of the afferent arteriole appeared to be highly modified. The smooth muscle cells at this site demonstrated a change in morphology and orientation, and the diameter of the arteriole was altered. The pattern of the vascular casts at the origin of the afferent arteriole varied from that portion at the glomerulus, suggesting a modification of the vascular wall near the renal corpuscle. Although the morphology of the renal microvasculature of the Black bear is similar to that of other mammals in some aspects, it is dissimilar to that of other carnivores and of the human kidney in that there are structural modifications of the afferent arteriole that may contribute to a reduction of blood flow to the nephron during winter sleep.     

Scanning and transmission electron-microscopic study of peripolar cells in the newborn lamb kidney

Scanning and transmission electron microscopy were used to study the ultrastructural characteristics and positions of granulated peripolar cells in newborn lamb kidney. Following tissue fixation by vascular perfusion in situ, the vascular pole region of the glomerulus was exposed for examination by scanning electron micoscopy following removal of the glomerular tuft. Peripolar cells were recognized by their surface morphology enabling their quantification and an assessment of the relationship of their position in the renal cortex. The prominent expression of peripolar cells in this species was confirmed. Almost every vascular pole examined revealed peripolar cells (405 out of 407; 99.5%) and thus, throughout the cortex, the distribution of peripolar cells was the same as the distribution of renal corpuscles. Larger, more protruding peripolar cells were observed in the outer cortical renal corpuscles. The numbers of peripolar cells encircling each vascular pole ranged from 1 to 10. There was no correlation between number of granulated peripolar cells at the vascular pole and the position of the renal corpuscle within the renal cortex. As viewed by transmission electron microscopy, organelles of protein synthesis were abundant in the cytoplasm of peripolar cells. Exocytosis of cytoplasmic granules was observed by both scanning and transmission electron microscopy implying that a process of regulative secretion occurs from these cells. The use of ultrastrural techniques has provided evidence supporting the concept that peripolar cells are prominent in the cuff region of each renal corpuscle of the newborn lamb and further-more that peripolar cells in this species most likely have a secretory function.     

The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus

Summary The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus (JGA) was reevaluated in rats, mice and Tupaia. Three ultrastructural features in the region of the vascular pole of the renal corpuscle are described that may be important for the fluid balance in this region: (1) podocyte foot processes in the parietal layer of Bowman's capsule, (2) endothelial fenestrations in the wall of the incoming afferent arteriole, both facing Goormaghtigh and epithelioid cells, and (3) the mesangial type lining of the glomerular stalk. With respect to the relevant pressure gradients, this morphology may provide the basis of bulk-fluid flow directed to the interstitium of the JGA including the Goormaghtigh cell field. Thus, the fluid balance in the lacis area and, consequently, the tubulo-glomerular feedback mechanism, probably does not solely depend upon the reabsorptive transport of the macula densa. Similar considerations may be valid for the humoral control of renin secretion from juxtaglomerular epithelioid cells.These studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres System     

Studies on the juxtaglomerular apparatus

The vascular pole of the juxtaglomerular apparatus in Tupaia belangeri was studied with special reference to the intercellular contacts of the periendothelial cells and the endothelium of the vas afferens. The periendothelial cells of the vascular pole of the glomerulum are connected by numerous gap junctions; and the granulated epithelial cells are suggested to form a functional unit. Probably there is a continuity of this system throughout the entire vascular pole including (1) all granulated cells, (2) all lacis cells, (3) the mesangium cells and (4) the adjacent smooth muscle cells of the vas afferens and vas efferens. Analysis of the endothelial junctions shows a zonular arrangement of tight junctions indicating a rather tight blood-tissue barrier next to the glomerular vascular pole; The ultrastructure of the different cell types of the vas afferens is also described, emphasizing the granulated epithelial cells and their innervation.     

Morphology of adrenergic and cholinergic innervation of the kidney as affected by spontaneous and ischemic renal hypertension in rats

The innervation of basic renal structures (vascular glomerular pole with juxtaglomerular apparatus and renal tubules) was experimentally studied in rats at different stages of spontaneous and Goldblatt hypertension. Both fluorescent determination of adrenergic innervation and histochemical identification of cholinergic innervation have shown that they increased in spontaneous and remained unchanged in renal hypertension. The data obtained confirm an important role of intrarenal innervation in the development of kidney "resettings" in spontaneous hypertension.     

Renal vasculature and uriniferous tubules in the common iguana

The pattern of vascular supply and the histology of uriniferous tubules of the kidney in the common iguana were studied by light microscopy of semithin sections and by scanning electron microscopy of microcorrosion casts. The corrosion casts showed a strongly developed renal portal system that forms an extensive capillary network throughout the kidney. Glomeruli are numerous and have a capillary pattern consisting of three to six loose coils of capillaries intercalated between afferent and efferent arterioles. Glomeruli are ovoid in shape and relatively small (mean diameter of the casts: 67 ± 19 μm in short axis and 79 ± 18 μm in long axis). Each glomerulus has a single afferent arteriole and efferent arteriole. The length and volume of the glomerular capillaries per unit volume of renal corpuscle are 0.0029 ± 0.0008 μm/μm³ and 0.321 ± 0.077, respectively. A short neck segment consisting of low epithelial cells is interposed between Bowman's capsule and the proximal tubule. A close association between the distal tubule and the glomerular hilus can be interpreted as a juxtaglomerular apparatus. © 1996 Wiley-Liss, Inc.     

Morphogenesis and ultrastructure of the peripolar cells in the mouse kidney.

Peripolar cells are located in the outer layer of the Bowman's capsule. They surround the vascular pole of the renal corpuscle and project into the urinary space. Morphologically they are characterized by the presence of secretory granules within their cytoplasm. In order to study their embryological development, we used 60 C57bl mice embryos (15th to 19th gestational day), 10 newborn mice (2 hours to 6 days old), 10 preadult mice (8-30 days old) and 4 adults (4 months old). Some granular cells, dispersed at the outer and inner layer of the Bowman's capsule, appear on the 17th gestational day. Later, these cells are found around the vascular pole of the renal corpuscle, located exclusively at the outer layer of the Bowman's capsule. Their granules are spherical and variously dense, they are surrounded by a membrane and their number increases progressively with time and reaches a maximum on the 4th postnatal day. Following that, there is a diminution and then their population stabilizes. By the end of the first month, there are only a few such cells (mean number 1 to 2). They become smaller and they always project into the urinary space.     

A comparative study of the glomerular peripolar cell and the renin-secreting cell in twelve mammalian species

The peripolar cell is a glomerular epithelial cell situated within Bowman's capsule at its vascular pole. It is believed to be a secretory cell which forms part of the juxtaglomerular apparatus. Scanning electron microscopy was used to perform a comparative study of the morphology and number of peripolar cells in twelve mammalian species. The number of renin-secreting cells in kidney sections stained by renin antibodies and immunocytochemistry was counted. There was a marked inter-species variation in the number, size and appearance of peripolar cells. They were largest and most abundant in sheep and goat and fewest in dog, cow and human. There was no correlation between the numbers of peripolar cells and renin-secreting cells. This does not support the view that the peripolar cell is part of the juxtaglomerular apparatus.     

Granulated peripolar epithelial cells in the renal corpuscle of marine elasmobranch fish

Summary Granulated epithelial cells at the vascular pole of the renal corpuscle, peripolar cells, have been found in the kidneys of five species of elasmobranchs, the little skate (Raja erinaced), the smooth dogfish shark (Mustelus canis), the Atlantic sharpnose shark (Rhizoprionodon terraenovae), the scalloped hammerhead shark (Sphryna lewini), and the cow-nosed ray (Rhinoptera bonasus). In a sixth elasmobranch, the spiny dogfish shark (Squalus acanthias), the peripolar cells could not be identified among numerous other granulated epithelial cells. The peripolar cells are located at the transition between the parietal epithelium of Bowman's capsule and the visceral epithelium (podocytes) of the glomerulus, thus forming a cuff-like arrangement surrounding the hilar vessels of the renal corpuscle. These cells may have granules and/or vacuoles. Electron microscopy shows that the granules are membrane-bounded, and contain either a homogeneous material or a paracrystalline structure with a repeating period of about 18 nm. The vacuoles are electron lucent or may contain remnants of a granule. These epithelial cells lie close to the granulated cells of the glomerular afferent arteriole. They correspond to the granular peripolar cells of the mammalian, avian and amphibian kidney. The present study is the first reported occurrence of peripolar cells in a marine organism or in either bony or cartilagenous fish.     

Ultrastructure of the renal corpuscle of Testudo graeca (Chelonia). A comparison between hibernating and non-hibernating animals

The renal corpuscle of hibernating and non-hibernating Testudo graeca was studied by means of light and electron microscopy. Renal corpuscles are small and have a glomerular architecture similar to that found in other vertebrates with a limited glomerular filtration rate. In hibernating animals, unlike non-hibernating, some morphological changes took place. The cells of the renal corpuscle were densely packed, podocytes and parietal cells showed a marked cytoplasmic vacuolization, there was a highly developed capillary basement membrane and the endothelial and mesangial cells showed abundant dense granules. These morphological features apparently correspond to a vacuolar degeneration. They may also be the morphological basis of the decrease in the glomerular filtration rate observed during this period.     

Physiological actions of angiotensin II on the kidney.

The importance of angiotensin as a modulator of renal function is well documented. Several lines of evidence suggest strongly that angiotensin plays an important role in the maintenance of renal vascular resistance and arterial pressure in several physiological and pathophysiological states with increased activity of the renin-angiotensin system. Angiotensin also acts as a physiological "brake" on excessive release of renin from juxtaglomerular cells. Angiotensin influences renal sodium excretion via its renal vascular actions to change the glomerular filtration rate and, thus, the filtered load of sodium; in addition, angiotensin influences tubular reabsorption of sodium by altering the filtration fraction and the balance of Starling forces in the peritubular capillaries.     

Effects of light and dark upon photoreceptor synapses in the retina of Xenopus laevis

Summary The adrenergic innervation of the juxtaglomerular complex was studied in kidneys from mice, rats, guinea-pigs, rabbits, cats, dogs, pigs, monkeys, and humans using fluorescence histochemistry of neuronal nor-adrenaline and autoradiography of ³H-noradrenaline. The localization of the nerves was established by phase contrast optics or by perfusing the vascular system with India ink. Adrenergic nerve terminals, exhibiting a formaldehyde-induced fluorescence and having the ability to take up and accumulate ³H-noradrenaline, were easily identified when they enclosed the glomerular afferent arteriole. They continued in between and close to the macula densa and lacis cells to supply the glomerular efferent arteriole. The nerves could be seen to accompany this arteriole for a considerable distance until they branched off to the vasa recta in the juxtamedullary region and to adjacent cortical veins. This innervation pattern was found to be a constant feature except in kidneys from guinea-pigs and cats, in which post-glomerular adrenergic nerves were not found in some of the superficial glomerular units. The fluorescence in all adrenergic fibres supplying the juxtaglomerular complex disappeared after removal of the aortico-renal ganglion, showing that they belong to a common system of renal sympathetic nerves.This work is dedicated to Professor Wolfgang Bargmann in honour of his seventieth birthday, January 26, 1976     

Renal vasculature and excretory system of the agamid lizard,Ctenophorus ornatus

The structure and ultrastructure of the vasculature and nephric tubules of the kidney of the Ornate Dragon Lizard, Ctenophorus (=Amphibolurus) ornatus, was investigated by light microscopy and scanning electron microscopy of resin casts. Compared with other agamid lizards, the arterial supply of only two arteries per kidney is small. The number of glomeruli per kidney in C. ornatus, at between 400 and 600, is low by reptilian standards and very low for lizards. The glomeruli are not only comparatively few in number but are also simple in the nature of their capillary configuration. These features are suggestive of a greatly reduced surface area for arterial filtration. In contrast to the small arterial supply, the afferent venous supply, the renal portal system (RPS), is substantial and forms an extensive capillary network throughout the kidneys. No venous shunts were found in the kidneys, suggesting that the venous network is functioning as a true portal system. Valves were not identified within the RPS, implying that neural control of general vascular tone could alter velocity and perhaps the direction of blood flow by changing pressure profiles. The nephroi are comparatively short and display features consistent with the production of urate precipitates as the primary nitrogenous waste product. A close association between the distal tubule (DT) and the glomerular hilus may demonstrate a simple form of a juxtaglomerular apparatus. The finding of aglomerular tubules indicates an important role for tubular secretion. The results of this study indicate that these lizards may have a reduced reliance on filtration for homoiostasis and a greater reliance on tubular secretion. © 1993 Wiley-Liss, Inc.     

Peripolar cells form the majority of granulated cells in the kidneys of antelopes and goats

Investigation of renal cortical tissue in 5 adult hartebeests (Alcelaphus buselaphus cokii), 3 impalas (Aepyceros melampus), 1 defassa waterbuck (Kobus defassa) and 5 goats (Capra hircus) revealed large granulated peripolar cells at the junction between the parietal and the visceral epithelial layers of the renal corpuscles. All four animal species under study contained 1 or more peripolar cells for the majority of renal corpuscles sectioned through the vascular pole. In the hartebeests, up to 3 parietal cells and the first podocyte were granulated. Peripolar cells contained intracytoplasmic electron-dense membrane-bounded granules-200-2,800 nm in diameter in the hartebeests, 200-1,740 nm in the impalas, 150-950 nm in the waterbuck and 200-2,140 nm in the goats. Epithelioid granulated juxtaglomerular cells around afferent and efferent arterioles were rarely seen. When observed, they contained smaller granules than those of the peripolar cells. This distribution suggests that peripolar cells play a role in the regulation of body electrolytes and water, probably acting in concert with the renin-angiotensin-aldosterone system.     

The nerves of the juxtaglomerular apparatus of man and other mammals contain the potent peptide NPY

The juxtaglomerular apparatus, a neuroendocrine unit located in the vascular pole of the glomerulus and influencing blood pressure by the secretion of renin, is known to have a rich supply of monoaminergic nerve fibres. Neuropeptide Tyrosine (NPY), a newly discovered, potent, vasoconstrictor peptide of 36 amino acids, has been found by immunocytochemistry to be present in a dense plexus of fibres around the juxtaglomerular apparatus of man, monkey, mouse, hamster, rat and guinea pig. NPY-immunoreactivity was markedly depleted after chemical sympathectomy by 6-hydroxydopamine. The concentration of NPY within the whole mouse kidney was 29.6 +/- 6.8 pmol/g and fractionation of the extracts demonstrated that the NPY-like immunoreactivity co-eluted from the column in the same position as the porcine NPY standard. The role of this peptide in renal physiology and pathology now needs urgent investigation.     

Continuity of the mesangial channel network with the glomerular basement membrane and intraglomerular subendothelial space

The composition and exact structure of the non-cellular mesangial matrix in the glomerulus of the human kidney are a matter of debate. It may appear like a structure similar to the glomerular basement membrane (GBM), it has been described to contain microfilaments. The exact transport route of fluids, solvents and immunocomplexes in the mesangium is not well-known either. We know that in some glomerular diseases immunocomplexes can be found in the GBM and the mesangium at the same time in the same patient. A possible explanation of the above findings could be provided by our hypothesis, i.e. the existence of a well-defined mesangial channel network (MChN). This MChN would consist of intercommunicating channels, which were embedded into the spongy cytoplasm of the mesangial cells (MCs) and surrounded by the plasma membrane of the mesangial cells. The MChN would lead from the subendothelial space through deep mesangium to the vascular pole or the juxtaglomerular apparatus and may transport fluid and other materials such as immunocomplexes into the mesangium. It would be continuous with the GBM. Microfilaments of the MC would be anchored to the walls of the MChN regulating its diameter, thus mesangial fluid transport and pressure. The dilatation of these channels by mechanical obstruction could contribute to glomerular sclerosis. The hypothesis can be challenged by methods like electronmicroscopy, immunoelectronmicroscopy, confocal laser-scanning microscopy, and vital stain studies. We provide some images suggesting the existence of the channel and its connection with the GBM. If the hypothesis was true, it could contribute to understanding of mesangial transport processes, pressure regulation and pathogenesis of glomerular mesangial diseases.     

Innervation of the renal vasculature of the toad (Bufo marinus)

The innervation of the dorsal aorta and renal vasculature in the toad (Bufo marinus) has been studied with both fluorescence and ultrastructural histochemistry. The innervation consists primarily of a dense plexus of adrenergic nerves associated with all levels of the preglomerular vasculature. Non-adrenergic nerves are occasionally found in the renal artery, and even more rarely near the afferent arterioles. Many of the adrenergic nerve profiles in the dorsal aorta and renal vasculature are distinguished by high proportions of chromaffin-negative, large, filled vesicles. Close neuromuscular contacts are common in both the renal arteries and afferent arterioles. Possibly every smooth muscle cell in the afferent arterioles is multiply innervated. The glomerular capillaries and peritubular vessels are not innervated, and only 3-5% of efferent arterioles are accompanied by single adrenergic nerve fibres. Thus, nervous control of glomerular blood flow must be exerted primarily by adrenergic nerves acting on the preglomerular vasculature. The adrenergic innervation of the renal portal veins and efferent renal veins may play a role in regulating peritubular blood flow. In addition, glomerular and postglomerular control of renal blood flow could be achieved by circulating agents acting via contractile elements in the glomerular mesangial cells, and in the endothelial cells and pericytes of the efferent arterioles. Some adrenergic nerve profiles near afferent arterioles are as close as 70 nm to distal tubule cells, indicating that tubular function may be directly controlled by adrenergic nerves.     

Immunolocalization of ecto-5'-nucleotidase in the kidney by a monoclonal antibody

A monoclonal antibody IgG, has been raised against ecto-5'-nucleotidase purified from rat kidney homogenate. The specificity of the antibody was verified by immunoprecipitation. The distribution of the corresponding antigen in the rat kidney was studied by immunocytochemistry (FITC and PAP technique) in 1 micron thick cryostat sections. The antibody reacted with the brush border of proximal tubules, the apical cell membrane and the apical cytoplasm of intercalated cells in connecting tubules and collecting ducts and with interstitial cells of the cortex. Among the interstitial cells exclusively stellate shaped fibroblasts were reactive whereas rounded interstitial cells (type II interstitial cells) as well as pericytes and endothelial cells of peritubular capillaries were unreactive. Compared to the staining intensity of the fibroblasts in the cortical labyrinth the reactivity of the fibroblasts in the medullary rays of the cortex was weak or absent. Interstitial cells of the entire medulla were unreactive. Concerning the fibroblasts in the periarterial connective tissue, those surrounding the larger arteries (arcuate arteries, cortical radial arteries) were negative, those alongside afferent and efferent arterioles were positive. Endothelia of lymphatic capillaries travelling within the periarterial connective tissue were also positive. All components of the juxtaglomerular apparatus were negative. The findings are consistent with an interstitial production of adenosine, available extracellularly and thus being able to reach the major target sites of adenosine, the smooth muscles of glomerular arterioles, including the granular cells at the glomerular vascular pole.     

The nerves of the juxtaglomerular apparatus of man and other mammals contain the potent peptide NPY

Summary The juxtaglomerular apparatus, a neuroendocrine unit located in the vascular pole of the glomerulus and influencing blood pressure by the secretion of renin, is known to have a rich supply of monoaminergic nerve fibres.Neuropeptide Tyrosine (NPY), a newly discovered, potent, vasoconstrictor peptide of 36 amino acids, has been found by immunocytochemistry to be present in a dense plexus of fibres around the juxtaglomerular apparatus of man, monkey, mouse, hamster, rat and guinea pig. NPY-immunoreactivity was markedly depleted after chemical sympathectomy by 6-hydroxydopamine. The concentration of NPY within the whole mouse kidney was 29.6±6.8 pmol/g and fractionation of the extracts demonstrated that the NPY-like immunoreactivity co-eluted from the column in the same position as the porcine NPY standard. The role of this peptide in renal physiology and pathology now needs urgent investigation.