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Nihon Hinyokika Gakkai Zasshi. the... Aug 1991To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological...
To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological experiments using mice. Adult male ICR strain mice weighing about 40 g were used. The mice were divided into 2 groups: the Cs group (Cs 50 mg/kg/day was orally given for 14 consecutive days) and the control group (olive oil for 14 days). Urine was stored for 24 hours on the day 0, 7 and 14 and urine volume and concentrations of urinary creatinine (u-Cr) and urinary potassium (u-K) were measured in each group. All the mice were sacrificed and examined on the 15th day. Concentrations of serum creatinine (s-Cr), serum potassium (s-K), plasma renin activity (PRA), plasma aldosterone (Ald) were noted in each group. The kidneys were also examined histologically with light and electron microscopes. The Cs group showed significant increases of s-K, PRA and Ald and a significant decrease of creatinine clearance compared with the control group. Histologically, the Cs group demonstrated focal vacuolar changes in the proximal tubular cells and an increase in the number of granules in the JG cells. Each granule of the Cs group was larger than that of the control group. Cs certainly stimulates the renin-angiotensin-aldosterone system and causes consequently a secondary aldosteronism.
Topics: Animals; Creatinine; Cyclosporine; Hyperaldosteronism; Juxtaglomerular Apparatus; Kidney; Male; Mice; Mice, Inbred ICR; Potassium; Renin
PubMed: 1921021
DOI: 10.5980/jpnjurol1989.82.1286 -
Cardiorenal Medicine 2021Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention... (Review)
Review
Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.
Topics: Chlorides; Diuretics; Heart Failure; Humans; Sodium; Water-Electrolyte Imbalance
PubMed: 33873189
DOI: 10.1159/000515604 -
Kidney International May 1975Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage. During and after total renal ischemia and acute...
Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage. During and after total renal ischemia and acute hemorrhage, renin activity in plasma (PRA) and microdissected juxtaglomerular apparatus (JGA) of rabbits were investigated. In controls, the apparent Michaelis-Mentoen constant (MMC) of semipurified standard renin of rabbits was 1025 plus or minus 223 SD ng/ml. Plasma renin of normal rabbits showed similar values: 1062 plus or minus 138 SD ng/ml. Intrarenal JGA renin, however, showed a great scatter of MMC (920 to 4760 ng/ml) and a significantly higher mean value of 2572 plus or minus 1156 SD ng/ml (pis less than 0.001). After complete renal ischemia by clamping both renal arteries for a 90-min period, the following results wereobtained: 1) Sixty min after the beginning of ischemia, PRA decreased from 20.9 plus or minus 9.8 SD to 7.6 plus or minus 5.2 SD ng/ml-hr (P is less than 0.05) and increased to 103, 68 and 42 ng/ml-hr 10, 30 and 90 min after removal of the clamps, respectively (P is less than 0.05).
Topics: Animals; Hemorrhage; Ischemia; Juxtaglomerular Apparatus; Kidney; Kidney Diseases; Ligation; Rabbits; Renal Artery; Renin
PubMed: 1133898
DOI: 10.1038/ki.1975.46 -
Hypertension (Dallas, Tex. : 1979) Aug 2020Juxtaglomerular cells are crucial for blood pressure and fluid-electrolyte homeostasis. The factors that maintain the life of renin cells are unknown. In vivo, renin...
Juxtaglomerular cells are crucial for blood pressure and fluid-electrolyte homeostasis. The factors that maintain the life of renin cells are unknown. In vivo, renin cells receive constant cell-to-cell, mechanical, and neurohumoral stimulation that maintain their identity and function. Whether the presence of this niche is crucial for the vitality of the juxtaglomerular cells is unknown. Integrins are the largest family of cell adhesion molecules that mediate cell-to-cell and cell-to-matrix interactions. Of those, β1-integrin is the most abundant in juxtaglomerular cells. However, its role in renin cell identity and function has not been ascertained. To test the hypothesis that cell-matrix interactions are fundamental not only to maintain the identity and function of juxtaglomerular cells but also to keep them alive, we deleted in vivo in cells of the renin lineage. In mutant mice, renin cells died by apoptosis, resulting in decreased circulating renin, hypotension, severe renal-vascular abnormalities, and renal failure. Results indicate that cell-to-cell and cell-to-matrix interactions via β1-integrin is essential for juxtaglomerular cells survival, suggesting that the juxtaglomerular niche is crucial not only for the tight regulation of renin release but also for juxtaglomerular cell survival-a sine qua non condition to maintain homeostasis.
Topics: Animals; Apoptosis; Cell Survival; Homeostasis; Integrin beta1; Juxtaglomerular Apparatus; Kidney Diseases; Mice; Mice, Knockout; Renal Artery; Renin
PubMed: 32594804
DOI: 10.1161/HYPERTENSIONAHA.120.14959 -
American Journal of Physiology. Renal... Oct 2018The secretion of the protease renin from renal juxtaglomerular cells is enhanced by subnormal extracellular calcium concentrations. The mechanisms underlying this...
The secretion of the protease renin from renal juxtaglomerular cells is enhanced by subnormal extracellular calcium concentrations. The mechanisms underlying this atypical effect of calcium have not yet been unraveled. We therefore aimed to characterize the effect of extracellular calcium concentration on calcium handling of juxtaglomerular cells and on renin secretion in more detail. For this purpose, we used a combination of experiments with isolated perfused mouse kidneys and direct calcium measurements in renin-secreting cells in situ. We found that lowering of the extracellular calcium concentration led to a sustained elevation of renin secretion. Electron-microscopical analysis of renin-secreting cells exposed to subnormal extracellular calcium concentrations revealed big omega-shaped structures resulting from the intracellular fusion and subsequent emptying of renin storage vesicles. The calcium concentration dependencies as well as the kinetics of changes were rather similar for renin secretion and for renovascular resistance. Since vascular resistance is fundamentally influenced by myosin light chain kinase (MLCK), myosin light chain phosphatase (MLCP), and Rho-associated protein kinase (Rho-K) activities, we examined the effects of MLCK-, MLCP-, and Rho-K inhibitors on renin secretion. Only MLCK inhibition stimulated renin secretion. Conversely, inhibition of MCLP activity lowered perfusate flow and strongly inhibited renin secretion, which could not be reversed by lowering of the extracellular calcium concentration. Renin-secreting cells and smooth muscle cells of afferent arterioles showed immunoreactivity of MLCK. These findings suggest that the inhibitory effect of calcium on renin secretion could be explained by phosphorylation-dependent processes under control of the MLCK.
Topics: Animals; Calcium; Calcium, Dietary; Juxtaglomerular Apparatus; Kidney; Mice; Myosin-Light-Chain Kinase; Phosphorylation; Renin; Urinary Tract Physiological Phenomena; rho-Associated Kinases
PubMed: 29357428
DOI: 10.1152/ajprenal.00554.2017 -
Kidney International Feb 2008Gap junctions are present in the juxtaglomerular apparatus enabling intercellular communication. Our study determined the location of different connexin subtypes within...
Gap junctions are present in the juxtaglomerular apparatus enabling intercellular communication. Our study determined the location of different connexin subtypes within the juxtaglomerular apparatus of the rat, and the role of these subtypes in renal hemodynamics through the use of specific mimetic peptides. Immunohistochemical analysis showed connexins 37 and 40 expression in the endothelial and renin-secreting cells of the afferent arteriole, while connexin 40 was also found in extra- and intraglomerular mesangial cells. In contrast, connexin 43 was weakly expressed in endothelial cells of the afferent arteriole and within the glomerulus. Intra-renal infusion of the peptides (GAP) reported to block specific gap junctions ((Cx37,43)GAP27 or (Cx40)GAP27), elevated blood pressure, plasma renin activity, and angiotensin II levels, while decreasing renal plasma flow without a significant change in the glomerular filtration rate. Subsequent restoration of blood pressure reduced both renal plasma flow and glomerular filtration rate. In contrast, (Cx43)GAP26 reduced glomerular filtration rate without alterations in blood pressure, renal plasma flow, plasma renin activity, or angiotensin II levels. Hence, connexins 37 and 40 are expressed in the rat juxtaglomerular apparatus and these proteins control, in part, the renin-angiotensin system and renal autoregulation.
Topics: Animals; Arterioles; Blood Pressure; Connexin 43; Connexins; Endothelium, Vascular; Gap Junctions; Glomerular Filtration Rate; Hemodynamics; Immunohistochemistry; Juxtaglomerular Apparatus; Kidney; Male; Rats; Rats, Inbred WKY; Renin-Angiotensin System; Gap Junction alpha-5 Protein; Gap Junction alpha-4 Protein
PubMed: 18046320
DOI: 10.1038/sj.ki.5002673 -
British Medical Journal Nov 1967
Topics: Adolescent; Alkalosis; Angiotensin II; Blood Pressure; Extracellular Space; Humans; Hyperaldosteronism; Hyperplasia; Hypokalemia; Juxtaglomerular Apparatus; Kidney Diseases; Male; Potassium; Renin; Sodium; Spironolactone
PubMed: 4293287
DOI: 10.1136/bmj.4.5575.327 -
The Tohoku Journal of Experimental... Feb 1964
Topics: Aldosterone; Angiotensins; Biomedical Research; Carcinoma, Hepatocellular; Cushing Syndrome; Hepatitis; Humans; Hyperaldosteronism; Hypertension; Hypertension, Malignant; Hypertension, Renal; Juxtaglomerular Apparatus; Kidney; Liver Cirrhosis; Liver Neoplasms; Nephrotic Syndrome; Pathology; Peritonitis; Physiology; Renin; Stomach Neoplasms
PubMed: 14136095
DOI: 10.1620/tjem.82.74 -
Kidney International. Supplement Sep 1998Tubuloglomerular feedback (TGF), which operates between the tubule and the parent glomerulus, is important to renal autoregulation and homeostasis of body fluid and... (Review)
Review
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.
Topics: Animals; Juxtaglomerular Apparatus; Organ Culture Techniques; Perfusion; Rabbits; Renal Circulation
PubMed: 9736252
DOI: 10.1046/j.1523-1755.1998.06709.x -
Kidney International Mar 2006Studies in patients with Bartter's and Gitelman's syndromes performed in the last 10 years have provided important insights into the mechanistic details of relevant... (Review)
Review
Studies in patients with Bartter's and Gitelman's syndromes performed in the last 10 years have provided important insights into the mechanistic details of relevant pathways of angiotensin II signaling and vascular tone regulation, therefore making these syndromes a good human model to gain insight into the mechanisms responsible for maintaining/controlling vascular tone. Extensive studies of patients with Bartter's/Gitelman's syndromes have, in fact, shown biochemical abnormalities of angiotensin II short- and long-term cell signaling, which depict a mirror image of those found in hypertension. The information obtained from the study of this human model of altered vascular tone regulation show that it can be used to gather more general data and/or confirm mechanistic details of the cellular and biochemical events involved in the pathophysiology of vascular tone control and to shed light on the multiplicity of the angiotensin II signaling-related mechanisms responsible for the pathophysiology of hypertension and its long-term complication such as cardiovascular remodeling and atherogenesis.
Topics: Angiotensin II; Bartter Syndrome; Blood Pressure; Blood Vessels; Calcium; Cardiovascular System; Endothelium, Vascular; GTP-Binding Proteins; Humans; Hypertension; Hypertrophy; Juxtaglomerular Apparatus; Magnesium; Oxidative Stress; Signal Transduction; Syndrome
PubMed: 16528244
DOI: 10.1038/sj.ki.5000253