泰和鸡肾小球旁器的观察

本文用光镜和透射电镜对泰和鸡(乌骨鸡)的肾小球旁器进行了观察。结果表明,泰和鸡的肾小球旁器由球旁细胞、过渡型致密斑、球外间膜细胞和极周细胞所组成。极周细胞在鸟类还属首次报道,它位于肾小囊脏层与壁层上皮移行处,环绕着肾小体的血管极,其结构与哺乳动物的相似。本文还就泰和鸡肾小球旁器的结构与功能的关系作了讨论。     

Functional morphology of the hypothalamo-neurohypophyseal system and juxtaglomerular apparatus in acute vascular insufficiency]

The functional morphology of the hypothalamic neurohypophyseal system (HNHS) and juxtaglomerular apparatus (JGA) were studied in 50 male cate. A rising secretory activity in HNHS and JGA, accompanied by accumulation of hormone-containing granules, was seen in acute vascular insufficiency caused both by the injection of a ganglion-blocking agent and by bloodletting. This factor is qualified by the authors as a specific sign of hypotonic stress, consisting in incomplete use of HNHS and JGA adaptive capacity in acute pressor hormone deficit.     

Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of hypertension

Although uncommon, presentation of juxtaglomerular cell tumor is distinct and should allow a correct preoperative diagnosis in most patients. Typical clinical presentations include headaches, polyuria, or isolated, asymptomatic, severe hypertension. The diagnosis of a juxtaglomerular apparatus (JGA) tumor typically results from identification of plasma renin levels two- to sevenfold greater than the normal value. Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated. Surgical excision is curative.     

Juxtaglomerular apparatus and interstitial cells of the kidney medulla after the administration of certain drugs and use of hyperbaric oxygenation

Electron microscopy was used to examine the status of the juxtaglomerular apparatus (JGA) and interstitial cells (IC) 3 and 24 hours after administration of furosemide (10 mg/kg), indomethacin (10 mg/kg), venoruton (500 mg/kg) and trental (100 mg/kg), and after 1,6 an 12 sessions of hyperbaric oxygenation. To evaluate objectively the results of examining the JGA, use was made of a method devised by the authors of a mathematical appraisal of granulation from the density of the epithelioid cells. Granulation of 50 IC from each animal was calculated on semi-thin araldite sections stained methylene blue-azur II-fuchsin. The results indicate that all the types of exposure including hyperbaric oxygenation produced JGA activation whose degree varied depending on the time elapsed after exposure. An apparently great increase in the JGA activity was detected after injection of furosemide and indomethacin. All the drugs with the exception of furosemide entailed granule accumulation after 3 hours, followed by the recovery of their amount after 24 hours. Furosemide injection produced a reverse effect.     

Connexin45 is expressed in the juxtaglomerular apparatus and is involved in the regulation of renin secretion and blood pressure

Connexin (Cx) proteins are known to play a role in cell-to-cell communication via intercellular gap junction channels or transiently open hemichannels. Previous studies have identified several connexin isoforms in the juxtaglomerular apparatus (JGA), but the vascular connexin isoform Cx45 has not yet been studied in this region. The present work aimed to identify in detail the localization of Cx45 in the JGA and to suggest a functional role for Cx45 in the kidney using conditions where Cx45 expression or function was altered. Using mice that express lacZ coding DNA under the control of the Cx45 promoter, we observed beta-galactosidase staining in cortical vasculature and glomeruli, with specific localization to the JGA region. Renal vascular localization of Cx45 was further confirmed with the use of conditional Cx45-deficient (Cx45fl/fl:Nestin-Cre) mice, which express enhanced green fluorescence protein (EGFP) instead of Cx45 only in cells that, during development, expressed the intermediate filament nestin. EGFP fluorescence was found in the afferent and efferent arteriole smooth muscle cells, in the renin-producing juxtaglomerular cells, and in the extra- and intraglomerular mesangium. Cx45fl/fl:Nestin-Cre mice exhibited increased renin expression and activity, as well as higher systemic blood pressure. The propagation of mechanically induced calcium waves was slower in cultured vascular smooth muscle cells (VSMCs) from Cx45fl/fl:Nestin-Cre mice and in control VSMC treated with a Cx45 gap mimetic peptide that inhibits Cx45 gap junctional communication. VSMCs allowed the cell-to-cell passage of the gap junction permeable dye Lucifer yellow, and calcium wave propagation was not altered by addition of the ATP receptor blocker suramin, suggesting that Cx45 regulates calcium wave propagation via direct gap junction coupling. In conclusion, the localization of Cx45 to the JGA and functional data from Cx45fl/fl:Nestin-Cre mice suggest that Cx45 is involved in the propagation of JGA vascular signals and in the regulation of renin release and blood pressure.     

Ultracytochemistry of Aminopeptidase A (angiotensinase A) in the kidney glomerulus and juxtaglomerular apparatus

Summary Ultracytochemical studies of the Aminopeptidase A (APA; angiotensinase A; E.C. 3.4.11.7) were performed on perfusion fixed rat and mouse kidneys (low-concentration aldehydes) using simultaneous azo coupling with -l-Glu-MNA as substrate and HPR as well as HNF as coupling agents. The studies of glomeruli and juxtaglomerular apparatus (JGA) show that APA is localized mainly at the cell membranes of podocytes and endothelial cells (rat and mouse) and of epitheloid cells (mouse) and Goormaghtigh's cells (rat). Increased APA activities are found in the region of cell contacts of epitheloid cells (mouse) and Goormaghtigh's cells (rat). In the epitheloid cells of mice, reaction product is also observed intracellularly in lysosomal structures. Concerning the functional significance of APA in the glomerulus and JGA, it would appear that this enzyme modifies or regulates angiotensin effects in the glomerulus and JGA through angiotensin degradation.Supported by the Deutsche Forschungsgemeinschaft (SFB 105)     

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.     

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     

Neuropeptide (neuropeptide Y,neurotensin, vasoactive intestinal polypeptide,substance P,calcitonin gene-related peptide,somatostatin) immunohistochemistry and ultrastructure of renal nerves

Summary With the use of several region-specific antisera and the peroxidase-antiperoxidase (PAP) technique, several regulatory polypeptides were localized in nerves of the kidney. Neuropeptide Y (NPY)- immunoreactivity (IR), neurotensin (NT)-IR and vasoactive intestinal polypeptide (VIP)-IR occurred at high densities in all segments of the renal arterial system forming a perivascular plexus. Furthermore, NT-IR nerves were particularly frequent at the juxtaglomerular apparatus (JGA). Calcitonin gene-related peptide (CGRP)-IR was mainly concentrated in nerves supplying the hilus arteries and the JGA. Substance P (SP)-IR was predominantly found in large varicosities close to large renal arterial vessels and in the vicinity of the JGA. Somatostatin (SOM)-IR was only observed in single varicosities located at the media-adventitia border of large renal hilus arteries. The peptidergic nerves are correlated to their ultrastructural counterpart. In addition, the distribution patterns and the frequency of the different types of renal peptidergic nerve fibres are evaluated and compared. The functional role of these neuropeptides and their origin within the efferent branch of this part of the peripheral autonomic nervous system is discussed. Furthermore, the implication of some of the neuropeptides studied in afferent renal innervation is also substantiated.Dedicated to Prof. Dr. T.H. Schiebler on the occasion of his 65th birthday     

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters.     

Neuropeptide (neuropeptide Y, neurotensin, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide, somatostatin) immunohistochemistry and ultrastructure of renal nerves

With the use of several region-specific antisera and the peroxidase-antiperoxidase (PAP) technique, several regulatory polypeptides were localized in nerves of the kidney. Neuropeptide Y (NPY)- immunoreactivity (IR), neurotensin (NT)-IR and vasoactive intestinal polypeptide (VIP)-IR occurred at high densities in all segments of the renal arterial system forming a perivascular plexus. Furthermore, NT-IR nerves were particularly frequent at the juxtaglomerular apparatus (JGA). Calcitonin gene-related peptide (CGRP)-IR was mainly concentrated in nerves supplying the hilus arteries and the JGA. Substance P (SP)-IR was predominantly found in large varicosities close to large renal arterial vessels and in the vicinity of the JGA. Somatostatin (SOM)-IR was only observed in single varicosities located at the media-adventitia border of large renal hilus arteries. The peptidergic nerves are correlated to their ultrastructural counterpart. In addition, the distribution patterns and the frequency of the different types of renal peptidergic nerve fibres are evaluated and compared. The functional role of these neuropeptides and their origin within the efferent branch of this part of the peripheral autonomic nervous system is discussed. Furthermore, the implication of some of the neuropeptides studied in afferent renal innervation is also substantiated.     

Radioprotective action of gas hypoxia (8%) in local irradiation of the kidneys]

The radioprotective action of hypoxia in local irradiation of kidneys was studied. The experiments were carried out on hybrid mice (CBA x C57Bl) exposed to local X-ray irradiation through a lead diaphragm matched to the kidneys. In the experimental group the animals breathed in gaseous mixture with 8% of oxygen prior to and during irradiation. 20-36 weeks after irradiation the functions of glomerular and juxtaglomerular systems, as well as mass of native and dried kidneys were studied in the animals. It is shown that hypoxia efficiently protects kidneys against irradiation and permits increasing the supplied dose of radiation at least by 25%. High-efficient protection is retained when passing from single to fractionated irradiation.     

Frequency of juxtaglomerular granulated cells in the mouse kidney.

Studies of 23 untreated adult mouse kidneys revealed that in mouse kidney sections the frequency of juxtaglomerular granulated cells as compared to the glomeruli is 38.5 +/- 1.79%, the value for the JGI, 71.8 +/- 3.93. Following 100 glomeruli through complete serial sections prepared from a single mouse kidney, it was shown that in the cortex of the mouse kidney all juxtaglomerular apparatus related to the glomeruli contain renin-producing modified smooth muscle cells with granulated cytoplasm.     

Effects of captopril on acute phase in two-kidney Goldblatt hypertensive rats and spontaneously hypertensive rats]

Effects of continuous oral administration of captopril were investigated on acute phase in two-kidney Goldblatt hypertensive (2 KGH) rats and spontaneously hypertensive rats (SHR). Systolic blood pressure gradually rose throughout the experimental period of 7, 14, 21 and 28 days in both 2 KGH rats and SHR. These gradual increases of systolic blood pressure were reduced by administration of captopril in both rats. Plasma renin activity were markedly increased throughout the experimental period in both rats treated with captopril, and were modestly increased in 2 KGH rats. In contrast, those changes in plasma renin activity were not obvious in SHR. In 2 KGH rats, juxtaglomerular index (JGI) and juxtaglomerular cell count (JGCC) of the clipped kidneys increased whereas JGI of the opposite kidneys decreased. In contrast, those changes in JGI and JGCC were not obvius in SHR. On the other hand, JGI and JGCC of the clipped kidneys increased in 2 KGH rats treated with captopril and those of the both kidneys increased in SHR treated with captopril. These results suggested that juxtaglomerular cells were related to the development of hypertension in 2 KGH rats, but were not clear in SHR. And these results were found that captopril showed antihypertensive effects, in spite of rises in JGI and JGCC of both 2 KGH rats and SHR.     

Angiotensin II in epitheloid (renin containing) cells of rat kidney

The PAP-method was used for immunocytochemical investigations with antisera against angiotensin (ang) I, ang II and renin in kidneys of rats and mice. In 14 rats, ang II was found in the media of the afferent arteriole - both in the region of the JGA and upstream until the interlobular artery. Serial sections alternately reacted for ang II and renin revealed that the octapeptide is contained in the well known renin positive epitheloid cells of the afferent arteriole and, beyond that, together with renin probably in the same "specific" granules. Fixation conditions were critical for the visualization of immunoreactivity With ang I antisera, comparable in terms of titer and affinity to the ang II antisera, specific immunoreactivity could not be found in the kidneys of rats. With horse radish peroxidase and ferritin as tracers it could be shown that the epitheloid cells of the JGA have the ability to pinocytize and incorporate macromolecules into their granules. It is suggested that ang II is taken up by these cells through the same route, Intracellular generation of ang II appears unlikely as an explanation. Functionally the selective uptake of ang II by epitheloid cells might be a specific process, possibly connected with the negative feedback of the octapeptide on renin secretion. Negative results in mice may be explained by a small uptake or more rapid degradation of ang II by the epitheloid cells.     

Immunohistochemical demonstration of renin in the juxtaglomerular apparatus of three Bufo species

Summary The cellular localization of renin was examined in the kidneys of some amphibians of the genus Bufo by immunoperoxidase and immunofluorescence techniques with an antiserum to renin isolated from the submandibular gland of the mouse. Immunoreactivity could be demonstrated in the media cells of the afferent arterioles (juxtaglomerular cells) close to as well as at great distance from the glomeruli. Occasionally, media cells of larger arterial vessels were also stained. The immunohistochemical data seem to be in accordance with earlier results obtained with a modified silver impregnation technique (Movat's staining procedure) used for the visualization of juxtaglomerular cells in non-mammalian vertebrates. Mouse kidney tissue, studied for purposes of comparison, showed renin-immunoreactivity as described by earlier investigators, i.e., immunoreactive staining in the afferent arterioles near the glomeruli and in the proximal tubule cells.     

Ultrastructure of mesangial and juxtaglomerular cells in the kidney of a hibernator

Summary The mesangial and juxtaglomerular cells were studied in kidneys of hibernating and non-hibernating ground squirrels, Citellus tridecemlineatus. In the hibernating animal, as compared with the non-hibernating, the mesangial cells show signs of increased activity. The cells are relatively larger, and numerous vacuoles appear in the cytoplasm. The juxtaglomerular cells also show signs of hyperactivity. Secretion droplets, mitochondria and free ribosomes increase in number and the endoplasmic reticulum becomes dilated. It is postulated that during hibernation, increased activity of mesangial cells slows glomerular filtration by absorption of filtrate into the mesangial matrix, and increased activity of juxtaglomerular cells results in increased renin secretion which in turn may stimulate hypersecretion of aldosterone to conserve sodium for water balance mechanisms necessary at the time.Supported by Research Grant A-2027 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health.We wish to gratefully acknowledge the technical assistance of Mary Gandia.     

The renin-angiotensin system in rats made hypertensive by ligation of the kidney poles (38584).

The renin-angiotensin system was studied in experimental renal hypertension produced by ligation of the poles of the left kidney followed by contralateral nephrectomy. Plasma renin concentration of renin substrate was lower and that of angiotensin I converting enzyme was higher in hypertensive animals. The juxtaglomerular index decreased in the medial zone of the kidney, while heavily granulated areas appeared in the poles. Ligated kidneys of rats that remained normotensive showed juxtaglomerular indices intermediate between the control and the hypertensive rats. Differences in renal renin content between the groups correspond to those for the juxtaglomerular index, but were smaller. No differences between the experimental groups were observed in iso-renin content in the brain; however in all animals with ligated kidney poles, hypertensive or normotensive, there was a tendency for iso-renin in the adrenals, left ventricular myocardium, and especially aorta to be lower than in controls.     

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     

Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys

We previously found that deletion of connexin 40 (Cx40) causes a misdirection of renin-expressing cells from the media layer of afferent arterioles to the perivascular tissue, extraglomerular mesangium, and periglomerular and peritubular interstitium. The mechanisms underlying this aberrant renin expression are unknown. Here, we questioned the relevance of cyclooxygenase-2 (COX-2) activity for aberrant renin expression in Cx40-deficient kidneys. We found that COX-2 mRNA levels were increased three-fold in the renal cortex of Cx40-deficient kidneys relative to wild-type (wt) kidneys. In wt kidneys, COX-2 immunoreactivity was minimally detected in the juxtaglomerular region, but renin expression was frequently associated with COX-2 immunoreactivity in Cx40-deficient kidneys. Treatment with COX-2 inhibitors for 1 wk lowered renin mRNA levels in wt kidneys by about 40%. In Cx40-deficient kidneys, basal renin mRNA levels were increased two-fold relative to wt kidneys, and these elevated mRNA levels were reduced to levels of untreated wt mice by COX-2 inhibitors. In parallel, renin immunoreactive areas were clearly reduced by COX-2 inhibitors such that renin expression vanished and decreased significantly in the periglomerular and peritubular extensions. Notably, COX-2 inhibitor treatment lowered plasma renin concentration (PRC) in wt kidneys by about 40% but did not affect the highly elevated PRC levels in Cx40-deficient mice. These findings suggest that aberrant renin-producing cells in Cx40-deficient kidneys express significant amounts of COX-2, which contribute to renin expression in these cells, in particular, those in the periglomerular and peritubular position. Apparently, these disseminated cells do not contribute to the enhanced renin secretion rates of Cx40-deficient kidneys.