Juxtaglomerular Granules Research Articles

Evidence for lysosomal matrix in the juxtaglomerular cell granules

A systematic histochemical analysis of the matrix composition of juxtaglomerular cell granules was carried out. The behaviour of kidney lysosomes under similar conditions has been examined in parallel. The tubular protein droplets produced by the i.p. administration of egg albumen were chosen as lysosome-model. Identical pattern of histochemical reactions has been demonstrated both in kidney lysosomes and juxtaglomerular granules indicating the presence of separate lipoprotein and glycoprotein components. The ammoniated silver carbonate method for lysosomes was also positive in juxtaglomerular cell granules. These results support on a non-enzymatic basis the concept that secretory granules and lysosomes are evolutionary homologues.

The juxtaglomerular apparatus in malignant hypertension of man.

Investigation of the behaviour of the renal juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area. In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing the production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division. In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the juxtaglomerular granulation index.

Tubular dimensions and juxtaglomerular granulation index in rat kidneys after unilateral obstruction of the ureter. A study of the morphogenesis of hydronephrosis.

The effect of ligation of a ureter on the tissues in the kidneys in male Wistar rats was studied by morphometry. Dilation of the lumen in the obstructed kidney persisted after ligation only in distal convolutions and collecting ducts. Swelling of epithelial cells in the obstructed kidney was noted only in the distal convolutions and collecting ducts. The Juxtaglomerular Granulation Index (JGI) in the obstructed kidney increased to a maximum 7 days after ligation of the ureter. In the control kidney the lumen of Bowman's space was expanded, epithelial cells in both proximal and distal parts of the nephron were swollen, and the JGI was increased after ligation of the contralateral ureter. The morphological findings support the assumption that reduced cortical blood flow and decreased intratubular flow are the cause of proximal tubular atrophy rather than a persisting increase of proximal intratubular pressure.

Ontogenesis of the renin-angiotensin system in spontaneously hypertensive and normal Wistar rats.

Kidney renin activity was investigated in spontaneously hypertensive and normotensive control Wistar rats. Kidneys were obtained from fetal rats after 18 and 21 days of gestation and from neonatal rats 1, 7, 14, and 21 days old. Kidney renin activity was determined by a modification of the radioimmunoassay for angiotensin I developed in this laboratory, and tissue from each age group was stained for juxtaglomerular granules. Kidney renin activity progressively increased in both strains from day 18 of fetal life until day 1 of neonatal life when a plateau level developed. In 1-day-old neonatal rats, significant differences in the kidney renin activity of the spontaneously hypertensive and the normotensive strains were initially noted. Kidney renin activity was maintained at significantly higher levels in the spontaneously hypertensive strain under 21 days of age when, because of a rise in the kidney renin activity of the normotensive control strain and a fall in the kidney renin activity of the spontaneously hypertensive strain, the difference between the two strains became statistically insignificant. In both strains, juxtaglomerular granules were first noted in 1-day-old neonatal rats and in each age group thereafter.

Juxtaglomerular cell granulation and renal cortical renin activity in normal and adrenalectomized guinea pigs.

In the normal guinea pig, the rennin activity of renal cortical tissue was one tenth of that of the rat. Light microscopy did not reveal juxtaglomerular granules in epitheloid cells, while electron mi

Renin and control of arterial blood pressure during terminal renal failure treated by haemodialysis and by transplantation.

1. Plasma renin concentrations were determined in 1068 samples obtained in 113 patients in the end stage of chronic renal failure treated by repeated haemodialyses or by renal transplantation. 2. Patients with malignant nephroangiosclerosis have a very high concentration of plasma renin; this differentiates them from other disease groups, where renin concentration is sometimes normal and sometimes elevated; there is no significant difference between the glomerulonephritis and pyelonephritis groups. 3. There is a weak but significant correlation between plasma renin concentration and arterial blood pressure. In the terminal stage of chronic renal insufficiency, blood pressure appears to be controlled by other quantitatively more important factors. However, the hypertension of some cases, characterized by high concentrations of plasma renin, can be controlled only by bilateral nephrectomy. 4. There is an inverse and highly significant correlation between plasma renin and sodium concentrations. This is also the case in transplanted patients where an inverse correlation also exists between plasma renin concentration and daily urinary output of sodium. 5. The juxtaglomerular granulation index correlates positively with the plasma renin concentration. 6. In terminal renal failure the kidney retains its capacity to secrete renin as a response to acute haemorrhage or other stimuli. 7. Renin is present in the blood of anephric patients and its concentration is not correlated either with the patient's sex or with the time elapsed after binephrectomy. 8. During rejection episodes in transplanted patients a rise of plasma renin concentration is frequently but not invariably observed. Elevation of plasma renin concentration is evident in very acute rejection crises.

Juxtaglomerular granules of the newborn rat kidney.

Differential centrifugation of newborn rat kidney homogenate produced a fraction containing juxtaglomerular granules. The granular fraction had a pressor activity 7.4 times higher per mg protein than the respective homogenate. Electron microscopy showed juxtaglomerular granules in both the epitheloid cells of the juxtaglomerular apparatus and the granular fraction. It is concluded that the concept of newborn rat kidney as an agranular model for the investigation of production and release of renin has to be modified.

Funktions- und Formwandel der Gefäßwandzellen des juxtaglomerulären Apparates der Niere beim Kaninchen

A solitary loss of blood and three subsequent orthostatical collapses in the rabbit are followed by a temporary anury and oligury. If the granular cells of the afferent arterioles are not injured too much, they answer after an initial, short depression of the juxtaglomerular granulation index with a forced de-novosynthesis. Rough-surfaced endoplasmic reticulum, golgi-complex and free ribosomes get well developed and the juxtaglomerular granulation index rises to the twofold of its normal value. Different shapes of granules represent various stages of maturity during the formation of the secret. Besides pure smooth muscle cells and granular cells there exists a further cell population in the vas afferens, which — due to functional necessity and with adequate structural differentiation — may act either more in a constringent or more in a secretory manner. The decrease of the granulation index during the state of reparation indicates the release of secretory material. The mechanism of this release ist not evident. Notable are the coagulation necroses of some strong granulated „epitheloid“ cells still 4 days after the acute injury. Ein einmaliger Blutverlust und mehrere anschliesende orthostatische Kollapse fuhren beim Kaninchen zu einer temporaren Anurie und Oligurie. Sind die granulierten epitheloiden Zellen des Vas afferens nicht zu stark geschadigt, so antworten sie nach einem initialen, kurzfristigen Absinken des juxtaglomerularen Granulationsindex mit einer forcierten de-novo-Synthese. Sie ausert sich nach einer starkeren Entfaltung des rauhen endoplasmatischen Reticulums, der Golgi-Felder und der freien Ribosomen in einem Anstieg des Granulationsindex auf das Zweifache der Norm. Unterschiede der Granulaformen sind Ausdruck der verschiedenen Reifungsstadien wahrend der Sekretbildung. Auser reinen glatten Gefasmuskelzellen und granulierten epitheloiden Zellen gibt es eine Zellpopulation, die — je nach der funktionellen Anforderung und bei entsprechender feinstruktureller Differenzierung — entweder mehr konstriktorisch oder mehr sekretorisch tatig sein kann. Der Abfall des Granulationsindex wahrend des Wiedererholungsstadiums ist Ausdruck der Sekretabgabe aus den granulierten epitheloiden Zellen. Der Mechanismus der Sekretausschleusung ist noch nicht geklart. Bemerkenswert sind Koagulationsnekrosen einzelner stark granulierter „epitheloider“ Zellen noch 4 Tage nach der akuten Schadigung.

Der juxtaglomeruläre Apparat der Rattenniere im Verlauf von Wachstum, Reifung und Alterung

The juxtaglomerular granulation index (the specific secretory ability of the vas afferens wall-cells) in the healthy unstressed rat shows age-specific quantitative, qualitative and topographic changes. These changes are motivated by cellular and functional, renal and extrarenal factors. At birth there are a few granules in the polar region of the more developed juxtamedullar glomerula, sparing the remaining cortex zones. After 20 days the production of secretion granules reaches its peak. Thereafter the granulation index gradually decreases and fluctuates towards the normal values of the adult rat. From the 3d to the 18th month it remains constant. Thereafter the ageing-process sets in : insufficiency in synthesis, in transport and in cell-division and specially a disturbance of cellmembrane-permeability. Further there is a reduction in the absorption ability of the with lysosomal residual bodies overloaded tubular epithelial cells. The juxtaglomerular granulation index is reduced to levels comparable to the newborn. The pattern of distribution differs during growth, maturation and ageing. The age specific changes of the granulated epitheloid cells correlate with those of the macula densa.

The renin-angiotensin system in newborn dogs.

A detailed evaluation of the rennin–angiotensin system by concurrent determinations of plasma renin activity, renal renin activity, and juxtaglomerular index in newborn dogs during the first 15 days of extrauterine life is described. Findings show that the plasma renin activity is significantly higher for the first 2 weeks of extrauterine life when compared with the values found in adult dogs, and that the renal renin activity is slightly greater despite a very low juxtaglomerular index with a few granular cells, mostly located in the juxtamedullary cortex. Stimulation (peritoneal dialysis) of renin release resulted in a marked increase in plasma renin activity. The juxtaglomerular index was not modified by the stimulation whereas the renal renin activity decreased slightly. From these results, it is suggested that the formation and secretion of renin is well developed in kidneys of newborn dogs despite the absence of demonstrable juxtaglomerular cell granules.

Juxtaglomerular granules in subcellular fractions of guinea-pig kidney.

The preparation of a subcellular fraction of renin-containing juxtaglomerular granules of guinea-pig kidney is described. Two separate preparations had a 8.4 and 15 times higher pressor activity [3] per mg protein than the respective homogenate. Electron microscopy showed mitochondria, non-specific and specific juxtaglomerular granules in the granular fraction. It is concluded, that the concept of adult guinea-pig kidney as an agranular model for the investigation of production and release of renin has to be modified.

An improved crystal violet method with alkaline differentiation for juxtaglomerular granules.

In the previous alkaline crystal violet method for selectively demonstrating juxtaglomerular (JG) granules (Harada 1971), the staining solution was found to be unstable. Subsequent testing has shown that the alkali is equally effective if applied after a nonalkalized aqueous solution of crystal violet has been applied for the staining, thus allowing stable stock solutions of the staining reagents to be used. The new procedure is as follows:Sections of 4 μ thickness from adult mouse kidney fixed in phosphate-buffered 10% formalin were cut from paraffin-embedded material and attached to slides with albumen adhesive. They were deparaffinized, hydrated, and washed in tap water.

Effects of sodium restriction on renin, norepinephrine, and cation content of cardiovascular tissues of dogs.

SummarySeven dogs were maintained for 1 month on a severely sodium-restricted diet. Another group of 4 dogs was maintained on the same dietary regimen with the addition of a “normal” NaCl supplement and served as controls. We studied: (a) renin activity in plasma (PRA). renal cortex (RRA), saphenous and mesenteric arteries (2nd to 5th branches), aorta, and left ventricle; (b) norepinephrine (NE) content of branches of mesenteric and saphenous arteries and veins, aorta, and left ventricle; (c) cation and water contents in saphenous, mesenteric (2nd to 5th branches), carotid and renal arteries, aorta, and left ventricle; (d) juxtaglomerular granulation index (JGI); (e) glucose-6-phosphate dehydrogenase (G6PD) activity in the cells of the adrenal zona glomerulosa. The most important findings were: (i) a significant increase of PRA and RRA and a slight, although not significant, increase in renin activity in the vascular tissues studied; (ii) a constant, but not significant, decrease in norepinephrine content...

Reactivity of juxtaglomerular granule cells to changes in sodium and potassium intake in the absence of the adrenal bodies.

Chez les rats adrenalectomises, une difference tres nette de l'indice de la granularite juxtaglomerulaire est apparue entre les animaux qui avaient bu du 2% NaCl et ceux qui avaient recu ou de l'eau distillee ou du 2% KCl. Il y a donc une reactivite juxtaglomerulaire, independente du cortex surrenal.

Rapid demonstration of juxtaglomerular granules with alcoholic crystal violet.

Adult mouse kidney fixed in 9 commonly used fixatives was embedded in paraffin, sections prepared as usual, and tests made with 16 different dyes (mostly triphenyl methanes) for efficacy in staining of juxtaglomerular granules. On the basis of the tests, staining of dewaxed and hydrated sections in 0.5% crystal violet in 70% ethanol for 3 min, rinsing in tap water, blotting and completion of dehydration in a 1:1 aniline-xylene mixture, clearing in xylene, and covering in a synthetic resin, is recommended. Tissues fixed in dichromate-containing fixatives required a prestaining oxidation with acidified KMnO4, but this was optional for other fixatives. In addition to crystal violet: ethyl violet, new fuchsin, and victoria blue 4R were also found to be effective stains for the granules.

Sodium Metabolism and Requirements in Lactating Rats

Sodium metabolism was studied in 4 groups of 11 lactating rats fed a diet containing either 0.03, 0.05, 0.07 or 0.09% sodium. Less feed intake, a loss in body weight and smaller pups at weaning were found with the group fed the 0.03% sodium compared with the 3 higher sodium groups. Plasma and bone sodium were lowest in the 0.03% sodium group following lactation, whereas no differences were found among the 3 higher sodium groups. There were no differences in blood cell volume or bone moisture among the groups. Milk samples taken on day 22 of lactation showed a higher fat content for the 0.03% sodium group, whereas the sodium concentration was significantly lower for the 0.03% than for the 0.09% group. Adrenal zona glomerulosa areas were largest for the 0.03% group, next largest for the 0.05% group and smallest for the 0.07 and 0.09% groups. Kidney juxtaglomerular granulation was greatest in the rats fed 0.03% sodium. With this nonpurified diet, 0.05% sodium was adequate for rats nursing 9 pups.

Effect of exogenous erythropoietin on juxtaglomerular cells.

SummaryExogenous erythropoietin (ESF) failed to influence indices of juxtaglomerular granules (JGI) or width of zona glomerulosa (ZGI) in normal rats or those subjected to hypoxia, unilateral renal artery constriction, or sodium depletion, stimuli associated with increased JGI and ZGI. Administration of renin, on the other hand, decreased JGI without reducing plasma ESF levels. These findings are interpreted as indirect evidence that the source of renal erythropoietin is not related to juxtaglomerular granules (JGG). Further, findings suggest that the increased JGI induced by hypoxia may be related to an increase in renal renin. Ultrastructural examination of JGG revealed their similar appearance in all situations suggesting that changes in JGI associated with various physiologic phenomena are most likely quantitative rather than qualitative.

Staining juxtaglomerular granules with basic fluorescent stains.

Many basic fluorescent dyes stain juxtaglomerular granules to produce characteristic colors in ultraviolet light. The stain is applied to paraffin sections of tissues fixed in 2% calcium acetate-10% formalin or in phosphate-buffered 10% formalin. Procedure: Bring section to water, stain 0.5 min in Delafield hematoxylin, wash in tap water, stain 3 min in a 0.1% aqueous solution of basic fluorescent dye (auramine O, acriflavine, acridine orange, coriphosphine O, acridine yellow, phosphine E, thioflavine T, berberine sulfate, atebrine or rivanol) and differentiate 1 min in 0.1% acetate acid (or omit this step). After washing in tap water, air dry with or without subsequent mounting in a resin. Juxtaglomerular granules stain bright fluorescent yellow or orange against a dark background.

The demonstration of renal juxtaglomerular granules and the evaluation of the index of granulation in the toad, Bufo bufo

1. A new method is described for the demonstration of granulated cells in the wall of the afferent arterioles in the toad kidney. After fixation in Bonin's fluid and embedding in paraffin, silver impregnation according to Movat was most successful in visualizing Juxtaglomerular granules in thin sections (2 μ). This method permits the evaluation of the index of granulation in a way comparable with that in the mammalian kidney. 2. The granulation index of toads immersed in saline (120 mE/1) for 10 days was lower than that of control animals. The significance of this phenomenon in the regulation of the salt balance in amphibia is discussed.

Relationship between serum renin concentration, renal renin content, and juxtaglomerular apparatus in hypertensive patients.

On a variety of 30 hypertensive patients and 3 controls, relationship between serum renin concentration, renal renin content, and juxtaglomerular apparatus (JGA) was studied. A highly significant correlation was found between serum renin concentration and renal renin content. The correlations between serum renin concentration and juxtaglomerular granulation index (JGI), and between renal renin content and JGI were also significant. The correlation coefficients, however, were significantly lower than that between serum renin and renal renin. Several factors including staining techniques may be related to this difference. From these results, it is concluded that renin levels are related to the changes in the JGA on a variety of hypertensive patients, although these relations are still problematic in a few cases.