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https://www.readbyqxmd.com/read/28424211/connecting-tubule-glomerular-feedback-mediates-tubuloglomerular-feedback-resetting-post-unilateral-nephrectomy
#1
Sumit R Monu, Yilin Ren, J X Masjoan Juncos, Kristopher Kutskill, Hong Wang, Nitin Kumar, Edward L Peterson, Oscar A Carretero
Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) Tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC)...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28407837/-effects-of-embryonic-lead-exposure-on-food-intake-and-bowel-movement-in-offspring-rats-and-possible-mechanisms
#2
Jian-Ping Zhou, Fan Wang, Xiao-Qing Yi, Xue-Ying Wang, Yong-Sheng Jiang, Yan Geng, Jing-Jing Wang
OBJECTIVE: To study the effects of embryonic lead exposure on food intake and bowel movement in offspring rats and possible mechanisms. METHODS: Sprague-Dawley rats were given 0.1% (low-dose lead exposure group) or 0.2% (high-dose lead exposure group) lead acetate freely during pregnancy to establish an animal model of embryonic lead exposure. A blank control group was also established. The male offspring rats were enrolled in the study, and 10 male offspring rats from each group were selected to observe the changes in food intake, bowel movement, gastric emptying, intestine propulsion, and pathological inflammatory response in the gastric mucosa...
April 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28381459/urinary-adenosine-excretion-in-type-1-diabetes
#3
Harindra Rajasekeran, Yuliya Lytvyn, Andrea Bozovic, Julie Lovshin, Eleftherios Diamandis, Daniel Cattran, Mansoor Husain, Bruce A Perkins, Andrew Advani, Heather N Reich, Vathany Kulasingam, David Z I Cherney
INTRODUCTION: In experimental models of diabetes, augmented sodium-glucose cotransport-2 (SGLT2) activity diminishes sodium (Na+) delivery at the macula densa. As a result, less vasoconstrictive adenosine is generated, leading to afferent arteriolar vasodilatation and hyperfiltration. The measurement and significance of urinary adenosine in humans has not been extensively examined in states of renal hemodynamic impairment, like that of diabetes. OBJECTIVE: Our aim was to validate a method for urine adenosine quantification in humans and perform an exploratory post-hoc analysis to determine whether urinary adenosine levels change dynamically in response to natriuresis in patients with type 1 diabetes (T1D) before and after treatment with the SGLT2 inhibitor (SGLT2i) empagliflozin...
April 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28351967/concerted-regulation-of-renal-plasma-flow-and-glomerular-filtration-rate-by-renal-dopamine-and-nos-i-in-rats-on-high-salt-intake
#4
Mariano E Ibarra, Maria F Albertoni Borghese, Mónica P Majowicz, María C Ortiz, Fabián Loidl, Manuel Rey-Funes, Luis A Di Ciano, Fernando R Ibarra
Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D1-like receptor antagonist SCH 23390 (1 mg kg bwt(-1) day(-1), sc) or a vehicle was administered...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28333068/effects-of-reactive-oxygen-species-on-tubular-transport-along-the-nephron
#5
REVIEW
Agustin Gonzalez-Vicente, Jeffrey L Garvin
Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA...
March 23, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28228405/inhibition-of-romk-blocks-macula-densa-tubuloglomerular-feedback-yet-causes-renal-vasoconstriction-in-anesthetized-rats
#6
Magali Araujo, William J Welch, Xiaoyan Zhou, Kathleen Sullivan, Shawn Walsh, Alexander Pasternak, Christopher S Wilcox
The Na+/K+/2Cl- cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide. Since outer medullary potassium channel (ROMK) inhibitors prevent reabsorption by NKCC2, we tested the hypothesis that ROMK inhibition with a novel, selective ROMK inhibitor (Compound C) blocks tubuloglomerular feedback (TGF) and reduces vascular resistance. Loop perfusion of either ROMK inhibitor or furosemide caused dose-dependent blunting of TGF, but the response to furosemide was 10-fold more sensitive (IC50= 10-6M for furosemide and IC50=10-5M for Compound C)...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27892876/low-expression-of-cyclooxygenase-2-in-chronic-kidney-disease-in-young-dogs
#7
Akira Yabuki, Akiko Miyazaki, Osamu Ichii, Moeko Kohyama, Mariko Sawa, Osamu Yamato
Chronic kidney disease (CKD) often results in end-stage renal failure in young dogs; however, the pathogenesis of this disease is not established. This study investigated renal expression of cyclooxygenase (COX)-1 and COX-2 proteins in three dogs with chronic kidney disease by immunohistochemistry. Histopathology showed asynchronous differentiation of renal tissues, including immature glomeruli. COX-1 signals were not detected in diseased or normal kidneys. COX-2 signals were low or undetectable in diseased kidneys, while normal kidneys showed clear positive signals in the macula densa (MD)...
December 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#8
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27508833/-op-7c-01-uromodulin-nacl-interaction-on-mrna-expression-of-ion-transporters-in-isolated-tubules-of-umod-and-umod-mice
#9
L Graham, D Graham, M W McBride, A F Dominiczak, S Padmanabhan
OBJECTIVE: UMOD-/- mice have low blood pressure and decreased salt-sensitivity indicating interactions between UMOD and sodium transport in the TAL. However, it's unclear whether the effect of UMOD is solely through interaction with cognate molecules in the TAL or whether the perturbations in physiology are more complex with involvement of both TAL and other parts of the nephron. We propose to answer this by profiling mRNA expression levels of the main ion transporters and signalling molecules in tubules from UMOD+/+ and UMOD-/- mice...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27478468/selected-tumor-markers-in-the-routine-diagnosis-of-chromophobe-renal-cell-carcinoma
#10
Anna M Badowska-Kozakiewicz, Michał P Budzik, Paweł Koczkodaj, Jacek Przybylski
Renal cell carcinoma is one of the most malignant tumors, affecting men more frequently than women and constituting nearly 90% of all kidney tumors. Chromophobe renal cell carcinoma has been described as a new histological type of renal cell carcinoma. Chromophobe renal cell carcinoma constitutes up to 5% of all cases of kidney cancer. It is characterized by a significant number of deletions in many chromosomes, as well as the loss of entire chromosomes. Chromophobe renal cell carcinoma arises from tubular cells or cells of the macula densa...
August 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27470878/sodium-glucose-cotransporter-2-inhibitors-in-the-treatment-of-diabetes-mellitus-cardiovascular-and-kidney-effects-potential-mechanisms-and-clinical-applications
#11
REVIEW
Hiddo J L Heerspink, Bruce A Perkins, David H Fitchett, Mansoor Husain, David Z I Cherney
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures by 4 to 6 and 1 to 2 mm Hg, respectively, which may underlie cardiovascular and kidney benefits...
September 6, 2016: Circulation
https://www.readbyqxmd.com/read/27306979/demonstration-of-the-functional-impact-of-vasopressin-signaling-in-the-thick-ascending-limb-by-a-targeted-transgenic-rat-approach
#12
Kerim Mutig, Tordis Borowski, Christin Boldt, Aljona Borschewski, Alexander Paliege, Elena Popova, Michael Bader, Sebastian Bachmann
The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear...
August 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27053689/distribution-of-organic-anion-transporters-nadc3-and-oat1-3-along-the-human-nephron
#13
Davorka Breljak, Marija Ljubojević, Yohannes Hagos, Vedran Micek, Daniela Balen Eror, Ivana Vrhovac Madunić, Hrvoje Brzica, Dean Karaica, Nikola Radović, Ognjen Kraus, Naohiko Anzai, Hermann Koepsell, Gerhard Burckhardt, Birgitta C Burckhardt, Ivan Sabolić
The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na(+)-K(+)-ATPase (EC 3.6.3.9), secondary active Na(+)-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs...
July 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/26972744/modeling-the-effects-of-positive-and-negative-feedback-in-kidney-blood-flow-control
#14
Runjing Liu, Anita T Layton
Blood flow in the mammalian kidney is tightly autoregulated. One of the important autoregulation mechanisms is the myogenic response, which is activated by perturbations in blood pressure along the afferent arteriole. Another is the tubuloglomerular feedback, which is a negative feedback that responds to variations in tubular fluid [Cl(-)] at the macula densa.(1) When initiated, both the myogenic response and the tubuloglomerular feedback adjust the afferent arteriole muscle tone. A third mechanism is the connecting tubule glomerular feedback, which is a positive feedback mechanism located at the connecting tubule, downstream of the macula densa...
June 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/26963840/expression-of-odc-antizyme-inhibitor-2-azin2-in-human-secretory-cells-and-tissues
#15
Tiina Rasila, Alexandra Lehtonen, Kristiina Kanerva, Laura T Mäkitie, Caj Haglund, Leif C Andersson
Ornithine decarboxylase (ODC) antizyme inhibitor 2 (AZIN2), originally called ODCp, is a regulator of polyamine synthesis that we originally identified and cloned. High expression of ODCp mRNA was found in brain and testis. We reported that AZIN2 is involved in regulation of cellular vesicle transport and / or secretion, but the ultimate physiological role(s) of AZIN2 is still poorly understood. In this study we used a peptide antibody (K3) to human AZIN2 and by immunohistochemistry mapped its expression in various normal tissues...
2016: PloS One
https://www.readbyqxmd.com/read/26903534/do-you-want-to-ditch-sodium-meet-nitric-oxide-synthase-1%C3%AE-at-the-macula-densa
#16
EDITORIAL
Pedro A Jose, William Welch
No abstract text is available yet for this article.
August 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/26883268/inhibition-of-nitric-oxide-synthase-1-induces-salt-sensitive-hypertension-in-nitric-oxide-synthase-1%C3%AE-knockout-and-wild-type-mice
#17
Ximing Wang, Kiran Chandrashekar, Lei Wang, En Yin Lai, Jin Wei, Gensheng Zhang, Shaohui Wang, Jie Zhang, Luis A Juncos, Ruisheng Liu
We recently showed that α, β, and γ splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1β accounts for most of the NO generation. We have also demonstrated that the mice with deletion of NOS1 specifically from the macula densa developed salt-sensitive hypertension. However, the global NOS1 knockout (NOS1KO) strain is neither hypertensive nor salt sensitive. This global NOS1KO strain is actually an NOS1αKO model. Consequently, we hypothesized that inhibition of NOS1β in NOS1αKO mice induces salt-sensitive hypertension...
April 2016: Hypertension
https://www.readbyqxmd.com/read/26848273/a-local-renal-renin-angiotensin-system-activation-via-renal-uptake-of-prorenin-and-angiotensinogen-in-diabetic-rats
#18
Akihiro Tojo, Satoshi Kinugasa, Toshiro Fujita, Christopher S Wilcox
The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/26823282/modulation-of-the-myogenic-mechanism-concordant-effects-of-no-synthesis-inhibition-and-o2-dismutation-on-renal-autoregulation-in-the-time-and-frequency-domains
#19
Nicholas G Moss, Tayler K Gentle, William J Arendshorst
Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [N(G)-nitro-l-arginine methyl ester (l-NAME)] reduced the time for complete autoregulation to 2 s and induced 0...
May 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/26647426/macula-densa-nitric-oxide-synthase-1%C3%AE-protects-against-salt-sensitive-hypertension
#20
Yan Lu, Jin Wei, David E Stec, Richard J Roman, Ying Ge, Liang Cheng, Eddie Y Liu, Jie Zhang, Pernille B Laerkegaard Hansen, Fan Fan, Luis A Juncos, Lei Wang, Jennifer Pollock, Paul L Huang, Yiling Fu, Shaohui Wang, Ruisheng Liu
Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, β-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1β expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1β expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1β mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice...
August 2016: Journal of the American Society of Nephrology: JASN
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