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Jurgen Schnermann - One of the best experts on this subject based on the ideXlab platform.
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Effect of Adenosinel-Receptor Blockade on Renin Release from Rabbit Isolated Perfused Juxtaglomerular Apparatus
2016Co-Authors: H Weihprecht, Jurgen Schnermann, John N Lorenz, Ole T Skett, Josie P. BriggsAbstract:Adenosine has been proposed to act within the Juxtaglomerular Apparatus (JGA) as a mediator of the inhibition of renin secre-tion produced by a high NaCi concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine, (Al)-receptor blocker 8-cyclopentyl-1,3-dipropyl-xanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The Al-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solu-tion at 10-1 M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (195 M) to the bath. Applied to the lumen, 10-5 M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P < 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10-7 and 10-5 M) in the bathing solution and in vehicle control experiments. The con-trol response to increasing luminal NaCI concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P < 0.01). It is concluded that Al-receptors are located within the JGA, and that Al-receptor activation inhibits renin release. A high NaCI concentration at the macula densa appears to influence Al-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion. (J. Clin. Invest. 1990. 85:1622-1628.) macula densa * kidney- adenosine analogue
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function of the Juxtaglomerular Apparatus control of glomerular hemodynamics and renin secretion
Seldin and Giebisch's The Kidney (Fifth Edition)#R##N#Physiology & Pathophysiology 1-2, 2013Co-Authors: Jurgen Schnermann, Hayo CastropAbstract:More than a century ago, Golgi observed that “the ascending limb of the loop of Henle returns with invariable constancy to its capsule of origin”. 1 At this point of contact at the glomerular hilum, the afferent and efferent arterioles together with the adherent distal tubule form a wedge-shaped compartment which contains the three defining cell types of the Juxtaglomerular Apparatus (JGA) ( Figure 23.1 ). The macula densa (MD) cells in the wall of the tubule abut on a cushion of closely packed interstitial cells called Goormaghtigh or lacis cells. These cells are indistinguishable in their fine structure from mesangial cells 2 and are also referred to as extraglomerular mesangial (EGM) cells. The third specialized cell type of the JGA is the Juxtaglomerular granular (JG) cell, a modified smooth muscle cell in the media of the arteriolar wall.
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effect of apocynin treatment on renal expression of cox 2 nos1 and renin in wistar kyoto and spontaneously hypertensive rats
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006Co-Authors: Alex Paliege, Jurgen Schnermann, A Parsumathy, Diane Mizel, Tianxin Yang, Sebastian BachmannAbstract: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 ...
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the Juxtaglomerular Apparatus from anatomical peculiarity to physiological relevance
Journal of The American Society of Nephrology, 2003Co-Authors: Jurgen SchnermannAbstract:Homer Smith died in 1962, the year before I started my career in the Department of Physiology of the University of Goettingen. At that time, his original work was still well known and widely quoted. Several decades later, this has of course changed, and the newer generation of renal physiologists
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Role of NO in the Function of the Juxtaglomerular Apparatus
Nitric Oxide and the Kidney, 1997Co-Authors: Jurgen Schnermann, Josie P. BriggsAbstract:Juxtaglomerular Apparatus (JGA) is the anatomical term for a conglomeration of specialized cells positioned at the vascular pole of the renal glomerulus. The constituents of this cell complex are epithelial, interstitial, and modified smooth muscle cells. The epithelial cells of the JGA are located at the distal end of the thick ascending limbs, a part of the nephron that always returns to the vascular pole of its parent glomerulus. The tubular cells in this contact area, called the macula densa (MD) cells, are cytologically distinct from the surrounding thick ascending limb cells. Underlying the MD cell plaque and filling the space between it and the arterioles is a cushionlike complex of specialized interstitial cells, called the extraglomerular mesangium (EGM). In their fine structure, EGM cells are similar to intraglomerular mesangial cells. EGM cells are coupled by an extensive network of gap junctions with each other. They are also coupled with vascular smooth muscle cells in the afferent arteriole and with the renin-containing granular cells in the media of the arteriolar wall. This anatomical arrangement is the probable route for a communication pathway along which changes in tubular fluid composition in the tubular lumen at the macula densa initiate successive alterations in the functional state of MD cells, EGM cells, and, finally, vascular smooth muscle and granular cells.
Janos Petipeterdi - One of the best experts on this subject based on the ideXlab platform.
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phenotypic dissection of the mouse ren1d knockout by complementation with human renin
Journal of Biological Chemistry, 2017Co-Authors: Charlotte Buckley, Janos Petipeterdi, Robert Nelson, Linda J Mullins, Matthew G F Sharp, Stewart Fleming, Christopher J Kenyon, Sabrina Semprini, Dominik Steppan, Armin KurtzAbstract:Normal renin synthesis and secretion is important for the maintenance of Juxtaglomerular Apparatus architecture. Mice lacking a functional Ren1d gene are devoid of renal Juxtaglomerular cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native cellular environment without confounding renin-angiotensin system interactions. A 55-kb transgene encompassing the human renin locus was crossed onto the mouse Ren1d-null background, restoring granulation in Juxtaglomerular cells. Correct processing of human renin in dense core granules was confirmed by immunogold labeling. After stimulation of the renin-angiotensin system, Juxtaglomerular cells contained rhomboid protogranules with paracrystalline contents, dilated rough endoplasmic reticulum, and electron-lucent granular structures. However, complementation of Ren1d-/- mice with human renin was unable to rescue the abnormality seen in macula densa structure. The Juxtaglomerular Apparatus was still able to respond to tubuloglomerular feedback in isolated perfused Juxtaglomerular Apparatus preparations, although minor differences in glomerular tuft contractility and macula densa cell calcium handling were observed. This study reveals that the human renin protein is able to complement the mouse Ren1d-/- non-granulated defect and suggests that granulopoiesis requires a structural motif that is conserved between the mouse Ren1d and human renin proteins. It also suggests that the altered macula densa phenotype is related to the activity of the renin-1d enzyme in a local Juxtaglomerular renin-angiotensin system.
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connexin45 is expressed in the Juxtaglomerular Apparatus and is involved in the regulation of renin secretion and blood pressure
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2008Co-Authors: Fiona Hanner, Julia Von Maltzahn, Stephan Maxeiner, Ildiko Toma, Arnold Sipos, Olaf Kruger, Klaus Willecke, Janos PetipeterdiAbstract: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 β-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.
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confocal imaging and function of the Juxtaglomerular Apparatus
Current Opinion in Nephrology and Hypertension, 2005Co-Authors: Janos PetipeterdiAbstract:Purpose of reviewMonitoring interactions between dissimilar cells is a key to understanding the function of the Juxtaglomerular Apparatus. This review will summarize new findings on tubuloglomerular feedback-mediated reductions in the glomerular filtration rate and renin release signals to elucidate
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two photon excitation fluorescence imaging of the living Juxtaglomerular Apparatus
American Journal of Physiology-renal Physiology, 2002Co-Authors: Janos Petipeterdi, Shigeru Morishima, Darwin P Bell, Yasunobu OkadaAbstract:Recently, multiphoton excitation fluorescence microscopy has been developed that offers important advantages over confocal imaging, particularly for in vivo visualization of thick tissue samples. We used this state-of-the-art technique to capture high-quality images and study the function of otherwise inaccessible cell types and complex cell structures of the Juxtaglomerular Apparatus (JGA) in living preparations of the kidney. This structure has multiple cell types that exhibit a complex array of functions, which regulate the process of filtrate formation and renal hemodynamics. We report, for the first time, on high-resolution three-dimensional morphology and Z-sectioning through isolated, perfused kidney glomeruli, tubules, and JGA. Time-series images show how alterations in tubular fluid composition cause striking changes in single-cell volume of the unique macula densa tubular epithelium in situ and how they also affect glomerular filtration through alterations in associated structures within the JGA. In addition, calcium imaging of the glomerulus and JGA demonstrates the utility of this system in capturing the complexity of events and effects that are exerted by the specific hypertensive autacoid angiotensin II. This imaging approach to the study of isolated, perfused live tissue with multiphoton microscopy may be applied to other biological systems in which multiple cell types form a functionally integrated syncytium.
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real time imaging of the living kidney Juxtaglomerular Apparatus with multiphoton microscopy
Multiphoton Microscopy in the Biomedical Sciences II, 2002Co-Authors: Janos Petipeterdi, Shigeru Morishima, P D Bell, Yasunobu OkadaAbstract:The process of glomerular filtrate formation and regulation of renal hemodynamics, including the tubuloglomerular feedback (TGF) mechanism from the macula densa (MD) and renin release, involves the complex interaction of a number of different cell types of the Juxtaglomerular Apparatus (JGA). It has been difficult to study these cellular interactions in living preparations given the constraints of existing technologies. Recently, two photon confocal laser microscopy has been developed that offers a tremendous increase in optical resolution versus conventional confocal microscopy. Importantly it can optically section through an entire glomerulus (glomerular diameter approximately equals 100 micrometers ). Thus, it provides the ability to directly study structures and cellular components that lie deep within the glomerulus. This new technology was used in our studies. We now report high-resolution images of various glomerular and JGA cells using the membrane-marker TMA-DPH and the calcium fluorophore indo-1. Time-series images show how alterations in tubular fluid composition cause striking changes in single cell volume of the macula densa tubular epithelium in situ and how it also affects glomerular filtration through alterations in associated structures within the JGA. Multi-photon excitation fluorescence microscopy in combination with isolated perfused JGA offers a powerful new tool to investigate the structural and cellular components that regulate the process of glomerular filtrate formation and renal hemodynamics.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Mitsumasa Nagase - One of the best experts on this subject based on the ideXlab platform.
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increased transforming growth factor β2 expression in the glomerular arteriole of the Juxtaglomerular Apparatus in a bartter s like syndrome
Human Pathology, 1999Co-Authors: Tatsuo Yamamoto, Tosiyuki Takahashi, Katsuhiko Yonemura, Katsuyuki Matsui, Mitsumasa NagaseAbstract:Abstract Although transforming growth factor-β (TGF-β) has been shown to participate in regulating hormone synthesis and release, little is known about involvement of individual human TGF-β isoforms, TGF-β1, -β2, and -β3, in renin synthesis and release. We examined expression of these TGF-β isoforms in a 50-year-old man with a Bartter's-like syndrome whose renal biopsy specimen showed hyperplasia of the Juxtaglomerular Apparatus (JGA), mild mesangial hypercellularity, focal tubular atrophy, and interstitial fibrosis. Immunoreactivity for renin and marked expression of TGF-β2 mRNA were noted in the glomerular arteriole of the JGA, whereas mRNA expression for TGF-β1 was only slight and that for TGF-β3 was still more faint. Expression of mRNAs for all 3 TGF-β isoforms was increased in the fibrotic interstitium. This expression pattern suggests that TGF-β2 may be involved in inducing renin synthesis and/or release in the glomerular arteriole of the JGA.
Sadayoshi Ito - One of the best experts on this subject based on the ideXlab platform.
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in vitro study of the Juxtaglomerular Apparatus and its implications in the chronic kidney disease
Hypertension, 2015Co-Authors: Sadayoshi ItoAbstract:The renin–angiotensin system (RAS) plays important roles in the regulation of renal functions and blood pressure (BP) and in the maintenance of homeostasis of electrolyte balance and body fluid composition under physiological conditions. For example, during dehydration and sodium depletion, specific actions of the RAS in the specific sites within the kidney are indispensable for maintenance of systemic circulation and glomerular filtration rate (GFR); thus, the RAS and complex renal structures and functions are essential components for survival. On the other hand, under pathological conditions, such as hypertension, diabetes mellitus, and chronic kidney disease, the RAS now becomes a villain that causes damages in the brain, heart, kidney, and vasculatures. Why is the RAS, a single system, beneficial for survival under one condition but harmful in other conditions? We may be able to find an answer in the process of the evolution of life.1–3 I have been engaged in the study of the RAS and renal hemodynamics from the basic and clinical aspects of hypertension and nephrology. In the basic study, I developed unique in vitro methods to directly study the function of the Juxtaglomerular Apparatus (JGA) that is composed of glomerular afferent and efferent arterioles and a plaque of specialized tubular epithelial cells called the macula densa.4–7 In the clinical research, together with many colleagues, I have performed large prospective cohort studies in chronic kidney disease and also large clinical trials in diabetic and nondiabetic nephropathy or hypertension.8–11 This review summarizes findings of our research on the RAS and renal hemodynamics together with other relevant literature, focusing on the structure–functional correlates of the kidney in relation to renal sodium handling and maintenance of GFR. In addition, I will describe a unique circulatory system commonly existing in vital organs, such as …
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characteristics of isolated perfused Juxtaglomerular Apparatus
Kidney International, 1998Co-Authors: Sadayoshi ItoAbstract:Characteristics of the isolated perfused Juxtaglomerular Apparatus. Tubuloglomerular feedback (TGF), which operates between the tubule and the parent glomerulus, is important to renal autoregulation and homeostasis of body fluid and electrolytes. The Juxtaglomerular Apparatus (JGA) has long been suggested as the anatomical site of TGF. To study the function of the JGA directly, we developed an in vitro preparation in which both the afferent arteriole (Af-Art) and macula densa (MD) of a microdissected rabbit JGA are microperfused simultaneously. We see that increasing the [NaCl] of the MD perfusate constricts the afferent arteriole in the segment close to the glomerulus. This constriction is blocked by furosemide, a loop diuretic known to inhibit TGF. On the other hand, microperfusion of Af-Arts alone showed the myogenic response to exist in the more proximal segments. Such an anatomical relationship between the myogenic response and TGF may enable the kidney to achieve its extremely efficient autoregulation.
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kidney and hypertension role of the Juxtaglomerular Apparatus
Tohoku Journal of Experimental Medicine, 1997Co-Authors: Sadayoshi ItoAbstract:The kidney plays an important role in the pathophysiology of hypertension. Recent studies suggest that glomerular hemodynamics may be critically involved not only in the pathogenesis of hypertension but also in the mode of progression of renal dysfunction. The Juxtaglomerular Apparatus (JGA), consisting of the glomerular afferent and efferent arterioles and the specialized tubular epithelial cells called the macula densa, plays a central role in the regulation of glomerular hemodynamics and renin release. This article reviews the mechanism by which the JGA controls renin release and glomerular hemodynamics as well as its relevance in the pathogenesis, pathophysiology and treatment of hypertension.
Michael Mauer - One of the best experts on this subject based on the ideXlab platform.
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Juxtaglomerular Apparatus t cell infiltration affects glomerular structure in type 1 diabetic patients
Diabetologia, 2004Co-Authors: R Moriya, J C Manivel, Michael MauerAbstract:Type 1 diabetes is an autoimmune disorder associated with T-cell mediated injury to multiple endocrine tissues. T-cell infiltration of the Juxtaglomerular Apparatus could be associated with changes in local renin angiotensin system activity and, thus, with changes in the renal microenvironment. We examined the frequency of Juxtaglomerular Apparatus T-cell infiltration early in Type 1 diabetes and tested whether this is associated with renal structure and function. We classified 89 Type 1 diabetic patients by immunohistochemical analysis as either Juxtaglomerular Apparatus T-cell positive (n=37) or T-cell negative (n=38). Borderline cases (n=14) were not considered further. T-cell positive patients had a shorter duration of diabetes (6.7±2.5 years) than T-cell negative patients (9.2±5.0 years, p=0.011) and lower albumin excretion rate, but they had a similar glomerular filtration rate and blood pressure. Renal biopsy morphometric analysis showed similar glomerular basement membrane width and mesangial fractional volume in these two groups. However, glomerular capillary surface density (p=0.0012) and filtration surface per glomerulus (p=0.0155) were greater in the T-cell positive patients. Increased filtration surface per glomerulus could be associated with glomerular filtration rate preservation in diabetes. Thus, Juxtaglomerular Apparatus immunologic injury in Type 1 diabetes patients could delay the clinical consequences of diabetic nephropathy.
