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Studies on the juxtaglomerular apparatus. V. The juxtaglomerular apparatus in Tupaia with special reference to intercellular contacts.

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.

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Anatomy of the juxtaglomerular apparatus.

The juxtaglomerular apparatus, located in the glomerular hilum, consists of a vascular component (afferent and efferent arterioles and extraglomerular mesangium) and a tubular component (macula densa). Two types of contact between vascular and tubular components are observed: a) a complex type, involving distal tubule, extraglomerular mesangium, and proximal efferent arteriole, and b) a simple type, consisting of apposition of the basement membranes of the vascular and tubular components. Juxtaglomerular granular cells, the source of renin, are present throughout the vascular component but are more numerous in the afferent arteriole. They can be considered as "myoendocrine" cells, since they contain myofibrils and attachment bodies, together with secretory granules and crystalline protogranules. Macula densa cells differ from those elsewhere in the distal tubule in that their nuclei are closer to each other, the Golgi apparatus is basally located, and their basal membrane infoldings are less prominent. Adrenergic nerves are demonstrable by fluorescence histochemistry in the juxtaglomerular region. Electron microscopy reveals unmyelinated nerve fibers containing small dense-cored vesicles and capable, as shown by ultrastructural autoradiography, of incorporating exogenous tritiated norepinephrine. Neuroeffector junctions occur between nerves and cells of the vascular and, less frequently, the tubular component. In addition, adrenergic axons are observed in a juxtaglomerular cell tumor. Nerve terminals are seen in direct contact with the tumor cells.

Acetylcholinesterase↗

Cell-specific protein and gene expression in the juxtaglomerular apparatus.

1. The juxtaglomerular apparatus (JGA) consists of a tubular component, the macula densa (MD), attached to a vascular component consisting of the afferent and efferent arterioles and the extraglomerular mesangium. The JGA is richly innervated by sympathetic fibres. 2. The MD is morphologically, histochemically and functionally different from the ascending thick portion of the loop of Henle where it is located. 3. The vascular component includes the vascular smooth muscle cells of the arteriole, the renin-producing cells or juxtaglomerular cells, extraglomerular mesangial cells (Goormaghtigh cells) and endothelial cells. They are coupled by gap junctions. 4. Physiological evidence indicates that the composition of tubular fluid at the MD regulates renin secretion and glomerular haemodynamics and that the JGA is important in the maintenance of body salt-water homeostasis. Evidence suggests that the MD exerts its action on the vascular component through a paracrine mechanism.

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Whys and wherefores of juxtaglomerular apparatus function.

The juxtaglomerular apparatus is an anatomic structure which links the distal end of the thick ascending limb at the macula densa with the glomerular vascular pole. Specialized interstital cells and renin containing granular cells are located in the vascular hilum at this site. Evidence has accumulated that this connection is critical for local regulation of renin secretion and glomerular vascular tone via the tubuloglomerular feedback mechanism. The tubuloglomerular feedback mechanism maintains a constant chloride concentration at the macula densa at a set point determined by the volume state of the animal, a effect probably important for adjustment of renin secretion to changing salt balance. Evidence supporting these two regulatory roles is reviewed here.

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The structure of the human juxtaglomerular apparatus. A morphometric, lightmicroscopic study on serial sections.

49 juxtaglomerular apparatuses were examined using 1.9mu thick Giemsa-stained serial sections from human renal tissue embedded in plexiglass. In 43 juxtaglomerular apparatus the direct contact areas between the different juxtaglomerular structures and the basal area of the macula densa were calculated. A positive, significant correlation was found between the size of the macula densa and the direct contact area between macula densa and Goormaghtigh's cell field on the one hand, and between the macula densa and the direct contact area between Goormaghtigh's cell field and the afferent arteriole on the other. There was also a significant, positive correlation between the direct contact area of Goormaghtigh's cell field with the macula densa and that of Goormaghtigh's cell field with the afferent arteriole. On the efferent side none of these correlations were significant. Thus a "flow of information" from the macula densa via the Goormaghtigh cells to the afferent arteriole is morphologically possible. The direct contact areas between macula densa and the afferent or the efferent arterioles were not correlated with any of the other parameters. Epithelioid cells were present in the interlobular arteries, prior to and within the juxtaglomerular apparatus in the afferent arterioles, as well as within and beyond the juxtaglomerular apparatus in the efferent arterioles.

Adult↗

Immunohistochemical localization of type IV collagen fibronectin and laminin in the juxtaglomerular apparatus of the rat kidney.

The juxtaglomerular apparatus (JGA) is a complex structure containing several components: the vessels, the extraglomerular mesangium and the distal tubule. These structures include cellular elements and an extracellular matrix (ECM). Collagenous (type IV collagen) and noncollagenous components of the basement membranes were studied. The localization of type IV collagen and of two extracellular glycoproteins (laminin and fibronectin) was investigated using immunofluorescent and immunoperoxidase labelled antibodies. Type IV collagen and laminin have the same localization on the JGA basement membranes. On the other hand, fibronectin is limited to the entrance of the glomerular stalk. On electron microscopy, type IV collagen is found in the basement membrane while fibronectin is restricted to certain areas of the extracellular matrix. These findings confirm data concerning the distribution of these three components in basement membranes and allow a better understanding of the histoarchitecture of the juxtaglomerular apparatus.

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The presence of a juxtaglomerular apparatus in elasmobranch fish.

UNLABELLED: Previous studies have concluded that a juxtaglomerular apparatus evolved in phylogenetic groups "higher" than elasmobranch fishes. The present study shows for the first time a distinct juxtaglomerular apparatus in four marine elasmobranchs, the spiny dogfish Squalus acanthias), the smooth dogfish (Mustelus canis), the little skate (Raja erinacea), and the cownose ray (Rhinoptera bonasus). Serial semithin sections of these fishes' kidneys reveal the four morphological components of a juxtaglomerular apparatus at the vascular pole of the renal corpuscle: (1) an afferent arteriole surrounded by smooth muscle cells which have granules containing a material exhibiting a periodic substructure comparable to that of renin granules in higher vertebrates; (2) an efferent arteriole usually devoid of smooth muscle cells but having pericyte-like cells; (3) a macula densa portion of the distal tubule juxtaposed between the afferent and efferent arterioles; and (4) elongated, fusiform cells (Goormaghtigh cells), which are in continuity with similar cells of the abundant intra-glomerular mesangium, and fill the space bordered by the distal tubule and by the afferent and efferent vessels. The distal tubule, from the site where it lies close to the afferent arteriole, moves directly toward the urinary pole, frequently indenting the renal corpuscle. Within this indentation, the tubule may be flanked by the efferent vessel, by the extraglomerular mesangium, or by Bowman's capsule only. Facing these structures the tubular epithelial cells possess basally dilated intercellular spaces. Endothelial cells of the efferent vessel(s) are fenestrated, possessing pores which are closed by a diaphragm. CONCLUSION: marine elasmobranch fish possess the morphological components of a juxtaglomerular apparatus which suggests that these fishes, like most other vertebrates, possess a renin-angiotensin system and a glomerular-tubular feedback mechanism.

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Active and inactive renin in individual juxtaglomerular apparatuses.

1. Renin was measured in individual juxtaglomerular apparatuses before and after acidification in vitro. 2. Active renin increased with delivery of extra sodium by microperfusion to the macula densa and this increase was similar to that achieved with acidification. 3. In rats pretreated with an inhibitor of protein synthesis active renin increased when extra sodium was delivered to the macula densa. 4. Salt intake changed the amount of renin present in the juxtaglomerular apparatus. In rats on a high salt intake the total renin was low and was all in an active form.

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Phospholemman expression in extraglomerular mesangium and afferent arteriole of the juxtaglomerular apparatus.

The molecular mechanisms with which the juxtaglomerular apparatus accomplishes its twin functions, acute regulation of glomerular blood flow and secretion of renin, are still not clearly understood. Least understood is the role of the extraglomerular mesangial (EM) cells, also known as lacis or Goormaghtigh cells, which lie sandwiched between the macula densa and the afferent and efferent arterioles. Here, we report that immunoreactivity for phospholemman (FXYD1), a single-span membrane protein homologous to the gamma (gamma) sub-unit of the Na,K-ATPase, is found in the kidney in EM cells with the Na,K-ATPase beta2-subunit and in cortical blood vessels and the afferent arteriole with Na,K-ATPase alpha2 and beta2. Phospholemman's distribution in EM cells is distinct from that of the Na,K-ATPase gamma-subunit, which is found on the basolateral surface of macula densa cells with Na,K-ATPase alpha1 and beta1. Phospholemman is a major kinase target, and its location in the juxtaglomerular apparatus suggests that it is involved in tubuloglomerular feedback.

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Renin immunocytochemistry of the differentiating juxtaglomerular apparatus.

The differentiation of the juxtaglomerular apparatus in fetuses and newborn mice was investigated by renin immunocytochemistry and electron microscopy. Three to four days before delivery and prior to other organs renin was found in the fetal kidney. At this early time immunoreactivity was preferentially located in cells of the media of interlobular arteries. In newborn mice the formation of new nephrons and maturation of their glomeruli was accompanied by a shift in renin localization from the interlobular arteries to the afferent arterioles. At the same time, kidney renin content and concentration increased rapidly. Synchronously with renin immunoreactivity, during the capillary loop stage of glomerular development, granulated epitheloid cells became visible in the afferent arteriole.

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[Ultrastructural cytochemistry of the mouse juxtaglomerular apparatus (author's transl)].

The ultrastructural cytochemistry of the mouse juxtaglomerular apparatus has been studied. The specific granules of the juxtaglomerular cells were found to be argentaphobic when ultrathin sections of araldite-embedded renal cortex were stained according to the periodic acid-thio-carbohydrazide-silver proteinate technique of Thiery. This technique revealed an abundant glycogen of type beta in the specific granules and in the cytosol of these cells. The rim of specific granules was positive when ultrathin sections of glutaraldehyde-fixed, glycol methacrylate-embedded kidneys were stained with phosphotungstic-hydrochloric acids at a low pH. A reaction was also shown by the cell coat, lysosomes, autophagolysosomes, residual bodies and part of the Golgi complex. These results indicate that the specific granules of the mouse juxtaglomerular apparatus contains glycoproteins that are glycosylated in the Golgi complex.

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Cellular mechanisms within the juxtaglomerular apparatus.

The tubular-vascular connection via the juxtaglomerular apparatus appears to serve two functions, local control of renal vascular resistance and regulation of renin secretion. A fall in single nephron glomerular filtration rate (SNGFR) and an increase in resistance are produced by an increase in NaCl concentration at the macular densa. This change also results in inhibition of secretion of renin. The macula densa has a unique location near the terminal end of the thick ascending limb, where NaCl concentration is highly flow dependent. The cellular mechanisms by which changes in tubular fluid NaCl produce vasoconstriction and inhibition of renin secretion are unknown, but the anatomy of the juxtaglomerular apparatus strongly suggests that such responses may be mediated by the extraglomerular mesangial cells located in the polar cushion underlying the macula densa. Recent evidence suggests that interstitial chloride concentration in this compartment may be quite variable, and that increases in external chloride may enhance the activation of the mesangial cell.

Feedback↗

Studies on the juxtaglomerular apparatus. IV. Freeze-fracturing of membrane surfaces.

The juxtaglomerular apparatus of the rat was studied after freeze-fracturing with special respect to intercellular junctions. It was found that juxtaglomerular granulated cells of the vas afferens are interconnected by gap junctions to adjacent cells (granulated cells, possibly also smooth muscle cells). Gap junctions have also been found on the surface of lacis cells and mesangial cells. It is therefore concluded that these cells of the juxtaglomerular apparatus and the glomerulus--granulated cells (possibly also smooth muscle cells) of the vas afferens, lacis cells and mesangium cells--form a functional system reacting in a coordinated manner to physiological stimuli.

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