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https://www.readbyqxmd.com/read/29735631/renal-specific-silencing-of-tnf-tumor-necrosis-factor-unmasks-salt-dependent-increases-in-blood-pressure-via-an-nkcc2a-na-k-2cl-cotransporter-isoform-a-dependent-mechanism
#1
Shoujin Hao, Mary Hao, Nicholas R Ferreri
We tested the hypothesis that TNF (tumor necrosis factor)-α produced within the kidney and acting on the renal tubular system is part of a regulatory mechanism that attenuates increases in blood pressure in response to high salt intake. Intrarenal administration of a lentivirus construct, which specifically silenced TNF in the kidney, did not affect baseline blood pressure. However, blood pressure increased significantly 1 day after mice with intrarenal silencing of TNF ingested 1% NaCl in the drinking water...
May 7, 2018: Hypertension
https://www.readbyqxmd.com/read/29687903/na-k-2cl-cotransporter-nkcc-physiological-function-in-nonpolarized-cells-and-transporting-epithelia
#2
Eric Delpire, Kenneth B Gagnon
Two genes encode the Na+ -K+ -2Cl- cotransporters, NKCC1 and NKCC2, that mediate the tightly coupled movement of 1Na+ , 1K+ , and 2Cl- across the plasma membrane of cells. Na+ -K+ -2Cl- cotransport is driven by the chemical gradient of the three ionic species across the membrane, two of them maintained by the action of the Na+ /K+ pump. In many cells, NKCC1 accumulates Cl- above its electrochemical potential equilibrium, thereby facilitating Cl- channel-mediated membrane depolarization. In smooth muscle cells, this depolarization facilitates the opening of voltage-sensitive Ca2+ channels, leading to Ca2+ influx, and cell contraction...
March 25, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29677005/maged2-a-novel-form-of-antenatal-bartter-s-syndrome
#3
Martin Kömhoff, Kamel Laghmani
PURPOSE OF REVIEW: Antenatal Bartter's syndrome (aBS) is the most severe form of Bartter's syndrome, requiring close follow-up, in particular during the neonatal period, primarily because of prematurity. The recent identification of a novel and very severe form of aBS merits an update on this topic. RECENT FINDING: Despite the identification of several genes involved in Bartter's syndrome, about 20% of patients clinically diagnosed with aBS remained without genetic explanation for decades...
April 18, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29672130/nadph-oxidase-4-derived-superoxide-mediates-flow-stimulated-nkcc2-activity-in-thick-ascending-limbs
#4
Fara Saez, Nancy J Hong, Jeffrey L Garvin
Luminal flow augments sodium reabsorption in the thick ascending limb more than can be explained by increased ion delivery. This segment reabsorbs 30% of the filtered load of sodium, playing a key role in its homeostasis. Whether flow elevations enhance Na/K/2Cl cotransporter (NKCC2) activity and the second messenger involved are unknown. We hypothesized that raising luminal flow augments NKCC2 activity by enhancing O2 - production by NADPH oxidase 4 (NOX4). NKCC2 activity was measured in thick ascending limbs perfused at either 5 or 20 nl/min with and without inhibitors of O2 - production...
April 19, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29561185/differences-in-renal-ammonia-metabolism-in-male-and-female-kidney
#5
Autumn N Harris, Hyun-Wook Lee, Gunars Osis, Lijuan Fang, Kierstin L Webster, Jill W Verlander, I David Weiner
Renal ammonia metabolism has a major role in the maintenance of acid-base homeostasis. Sex differences are well recognized as an important biological variable in many aspects of renal function, including fluid and electrolyte metabolism. However, sex differences in renal ammonia metabolism have not been previously reported. Therefore, the purpose of the current study was to investigate sex differences in renal ammonia metabolism. We studied 4-month-old wild type C57BL/6 mice fed a normal diet. Despite similar levels of food intake, and thus protein intake, which is the primary determinant of endogenous acid production, female mice excreted greater amounts of ammonia, but not titratable acids, than did male mice...
March 21, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29541861/internalization-of-nkcc2-is-impaired-in-thick-ascending-limb-of-henle-in-moesin-knockout-mice
#6
Kotoku Kawaguchi, Ryo Hatano, Mitsunobu Matsubara, Shinji Asano
Moesin is expressed in several types of cells including epithelial and endothelial cells. Several groups reported that moesin plays important roles in the regulation of the cellular motility, and the process of internalization of membrane proteins. However, the physiological roles of moesin in the kidney still remain unclear. Herein, we examined the physiological function of moesin in the kidney using moesin knockout (Msn -/y ) mice. There was no obvious abnormality in the renal morphology of Msn -/y mice. However, we found that Msn -/y mice exhibited mild hyperchloremia, and reduced glomerular filtration rate compared to wild type (WT) mice...
March 15, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29510178/metformin-increases-urinary-sodium-excretion-by-reducing-phosphorylation-of-the-sodium-chloride-cotransporter
#7
Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
OBJECTIVE: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys. METHODS: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin...
March 3, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29476644/axial-and-cellular-heterogeneity-in-electrolyte-transport-pathways-along-the-thick-ascending-limb
#8
REVIEW
H Dimke, J Schnermann
The thick ascending limb (TAL) extends from the border of the inner medulla to the renal cortex, thus ascending through regions with wide differences in tissue solute and electrolyte concentrations. Structural and functional differences between TAL cells in the medulla (mTAL) and the cortex (cTAL) would therefore be useful to adapt TAL transport function to a changing external fluid composition. While mechanisms common to all TAL cells play a central role in the reclamation of about 25% of the NaCl filtered by the kidney, morphological features, Na+ / K+ -ATPase activity, NKCC2 splicing and phosphorylation do vary between segments and cells...
May 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29436285/m%C3%A3-ni%C3%A3-re-s-disease-pathophysiology-endolymphatic-sac-immunohistochemical-study-of-aquaporin-2-v2r-vasopressin-receptor-nkcc2-and-trpv4
#9
Marc-Henri Asmar, Louis Gaboury, Issam Saliba
Objectives Endolymphatic sac (ELS) pathophysiology in Ménière's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin-2 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops...
April 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29416622/mntbap-therapy-attenuates-the-downregulation-of-sodium-transporters-in-obstructive-kidney-disease
#10
Mi Liu, Yangyang Zhu, Ying Sun, Zhaoying Wen, Songming Huang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Yue Zhang
Ureteral obstruction is associated with reduced expressions of renal sodium transporters, which contributes to impaired urinary concentrating capacity. In this study, we employed a synthetic mitochondrial superoxide dismutase 2 (SOD2) mimic MnTBAP to investigate the role of mitochondrial oxidative stress in modulating the sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters including NHE3, NCC, NKCC2, and ENaCα was observed as determined by qRT-PCR, Western Blotting or immunohistochemistry...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412704/with-no-lysine-kinase-4-modulates-sodium-potassium-2-chloride-cotransporter-activity-in-vivo
#11
Andrew Scott Terker, Maria Castaneda-Bueno, Mohammed Zubaerul Ferdaus, Ryan J Cornelius, Kayla J Erspamer, Xiao-Tong Su, Lauren N Miller, James A McCormick, Wen-Hui Wang, Gerardo Gamba, Chao-Ling Yang, David H Ellison
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4-/- mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29407172/nephron-segment-specific-gene-expression-using-aav-vectors
#12
Laureano D Asico, Santiago Cuevas, Xiaobo Ma, Pedro A Jose, Ines Armando, Prasad R Konkalmatt
AAV9 vector provides efficient gene transfer in all segments of the renal nephron, with minimum expression in non-renal cells, when administered retrogradely via the ureter. It is important to restrict the transgene expression to the desired cell type within the kidney, so that the physiological endpoints represent the function of the transgene expressed in that specific cell type within kidney. We hypothesized that segment-specific gene expression within the kidney can be accomplished using the highly efficient AAV9 vectors carrying the promoters of genes that are expressed exclusively in the desired segment of the nephron in combination with administration by retrograde infusion into the kidney via the ureter...
February 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29357410/tamm-horsfall-protein-uromodulin-deficiency-elicits-tubular-compensatory-responses-leading-to-hypertension-and-hyperuricemia
#13
Yan Liu, David Goldfarb, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Expression of Tamm-Horsfall protein (THP or uromodulin) is highly restricted to the kidneys' thick ascending limb (TAL) of loop of Henle. Despite the unique location and recent association of THP gene mutations with hereditary uromodulin-associated kidney disease and THP single nucleotide polymorphisms with chronic kidney disease and hypertension, the physiological function(s) of THP and its pathological involvement remain incompletely understood. By studying age-dependent changes of THP knockout (KO) mice, we show here that young KO mice had significant salt and water wasting but were partially responsive to furosemide, due to decreased luminal translocation of Na-K-Cl cotransporter 2 (NKCC2) in the TAL...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29251736/pge-2-ep-1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#14
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29145399/point-mutation-in-d8c-domain-of-tamm-horsfall-protein-uromodulin-in-transgenic-mice-causes-progressive-renal-damage-and-hyperuricemia
#15
Lijie Ma, Yan Liu, Nichole K Landry, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance...
2017: PloS One
https://www.readbyqxmd.com/read/29122955/dnpep-is-not-the-only-peptidase-that-produces-spak-fragments-in-kidney
#16
Rainelli Koumangoye, Eric Delpire
SPAK (STE20/SPS1-related proline/alanine-rich kinase) regulates Na+ and Cl- reabsorption in the distal convoluted tubule, and possibly in the thick ascending limb of Henle. This kinase phosphorylates and activates the apical Na-Cl cotransporter in the DCT. Western blot analysis reveals that SPAK in kidney exists as a full-length protein as well as shorter fragments that might affect NKCC2 function in the TAL. Recently, we showed that kidney lysates exerts proteolytic activity towards SPAK, resulting in the formation of multiple SPAK fragments with possible inhibitory effects on the kinase...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29100270/albuminuria-confers-renal-resistance-to-loop-diuretics-via-the-stimulation-of-nlrp3-inflammasome-prostaglandin-signaling-in-thick-ascending-limb
#17
Yibo Zhuang, Zhanjun Jia, Caiyu Hu, Guixia Ding, Xintong Zhang, Yue Zhang, Guangrui Yang, Rajeev Rohatgi, Songming Huang, John Ci-Jiang He, Aihua Zhang
Renal resistance to loop diuretics is a frequent complication in a number of kidney disease patients with elusive mechanism. Employing human renal biopsy specimens, albumin overload mouse model, and primary cultures of mouse renal tubular cells, albuminuria effect on NKCC2 expression and function and the underlying mechanisms were investigated. In the renal biopsy specimens of albuminuric patients, we found that NKCC2 was significantly downregulated with a negative correlation with albuminuria severity as examined by immunohistochemistry...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046296/geraniin-is-a-diuretic-by-inhibiting-the-na-k-2cl-cotransporter-nkcc2
#18
Erika Moreno, Juan A Gayosso, José R Montejano, Georgina Almaguer, Norma Vázquez, Cristino Cruz, Adriana Mercado, Norma A Bobadilla, Gerardo Gamba, Alfredo Sierra, Victoria Ramírez
Geranium seemannii Peyr is a perennial plant endemic to central Mexico that has been widely used for its diuretic effect, but the responsible compound of this effect is unknown as well as the mechanism by which the diuretic effect is achieved. Geraniin is one of the compounds isolated from this kind of geranium. This study was designed to determinate whether geraniin possesses diuretic activity and to elucidate the mechanism of action. Geraniin was extracted and purified from Geranium seemannii Peyr. Male Wistar rats were divided into four groups: 1) Control, 2) 75 mg/kg of geraniin, 3) 20 mg/kg of furosemide, and 4) 10 mg/kg of hydrochlorothiazide...
February 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28951728/urinary-exosomes-and-their-cargo-potential-biomarkers-for-mineralocorticoid-arterial-hypertension
#19
REVIEW
Eric R Barros, Cristian A Carvajal
Arterial hypertension (AHT) currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28940314/dietary-sodium-induces-a-redistribution-of-the-tubular-metabolic-workload
#20
Khalil Udwan, Ahmed Abed, Isabelle Roth, Eva Dizin, Marc Maillard, Carla Bettoni, Johannes Loffing, Carsten A Wagner, Aurélie Edwards, Eric Feraille
KEY POINTS: Body Na(+) content is tightly controlled by regulated urinary Na(+) excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na(+) intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na(+) intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na(+) transporters all along the kidney tubule. Low dietary Na(+) intake increased Na(+) reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments...
November 15, 2017: Journal of Physiology
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