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https://www.readbyqxmd.com/read/27892876/low-expression-of-cyclooxygenase-2-in-chronic-kidney-disease-in-young-dogs
#1
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)...
September 13, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#2
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...
November 22, 2016: 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/26634699/effect-of-cyclooxygenase-cox-1-and-cox-2-inhibition-on-furosemide-induced-renal-responses-and-isoform-immunolocalization-in-the-healthy-cat-kidney
#15
L Pelligand, N Suemanotham, J N King, W Seewald, H Syme, K Smith, P Lees, J Elliott
BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats...
2015: BMC Veterinary Research
https://www.readbyqxmd.com/read/26367377/effect-of-acetazolamide-on-obesity-induced-glomerular-hyperfiltration-a-randomized-controlled-trial
#16
RANDOMIZED CONTROLLED TRIAL
Boris Zingerman, Michal Herman-Edelstein, Arie Erman, Sarit Bar Sheshet Itach, Yaacov Ori, Benaya Rozen-Zvi, Uzi Gafter, Avry Chagnac
AIMS: Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied...
2015: PloS One
https://www.readbyqxmd.com/read/26269519/shear-stress-blunts-tubuloglomerular-feedback-partially-mediated-by-primary-cilia-and-nitric-oxide-at-the-macula-densa
#17
Lei Wang, Chunyu Shen, Haifeng Liu, Shaohui Wang, Xinshan Chen, Richard J Roman, Luis A Juncos, Yan Lu, Jin Wei, Jie Zhang, Kay-Pong Yip, Ruisheng Liu
The present study tested whether primary cilia on macula densa serve as a flow sensor to enhance nitric oxide synthase 1 (NOS1) activity and inhibit tubuloglomerular feedback (TGF). Isolated perfused macula densa was loaded with calcein red and 4,5-diaminofluorescein diacetate to monitor cell volume and nitric oxide (NO) generation. An increase in tubular flow rate from 0 to 40 nl/min enhanced NO production by 40.0 ± 1.2%. The flow-induced NO generation was blocked by an inhibitor of NOS1 but not by inhibition of the Na/K/2Cl cotransporter or the removal of electrolytes from the perfusate...
October 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/26180241/ultrastructural-and-immunohistochemical-localization-of-plasma-membrane-ca2-atpase-4-in-ca2-transporting-epithelia
#18
R Todd Alexander, Megan R Beggs, Reza Zamani, Niels Marcussen, Sebastian Frische, Henrik Dimke
Plasma membrane Ca(2+)-ATPases (PMCAs) participate in epithelial Ca(2+) transport and intracellular Ca(2+) signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca(2+) channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca(2+) flux and investigated the localization and regulation of Pmca4 in Ca(2+)-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes...
October 1, 2015: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/26169542/fetal-tubuloglomerular-feedback-in-an-ovine-model-of-mild-maternal-renal-disease
#19
Anita J Turner, Russell D Brown, Amanda Boyce, Karen J Gibson, A Erik G Persson
Fetuses of pregnant ewes, which were subtotally nephrectomized prior to mating, were studied to assess whether mild maternal renal impairment would affect fetal tubuloglomerular feedback (TGF) under control conditions and after the inhibition of macula densa-derived nitric oxide (NO). Based on previous observations we hypothesized that, the TGF curve of fetuses of subtotally nephrectomized (STNx) ewes would resemble that of a volume expanded fetus with a high production rate of NO and that inhibition of neuronal nitric oxide synthase (nNOS) would increase the sensitivity of the TGF system in these fetuses...
July 2015: Physiological Reports
https://www.readbyqxmd.com/read/26109090/parameter-estimation-for-mathematical-models-of-a-nongastric-h-na-k-nh4-atpase
#20
Mónica Nadal-Quirós, Leon C Moore, Mariano Marcano
The role of nongastric H(+)-K(+)-ATPase (HKA) in ion homeostasis of macula densa (MD) cells is an open question. To begin to explore this issue, we developed two mathematical models that describe ion fluxes through a nongastric HKA. One model assumes a 1H(+):1K(+)-per-ATP stoichiometry; the other assumes a 2H(+):2K(+)-per-ATP stoichiometry. Both models include Na+ and NH4+ competitive binding with H+ and K+, respectively, a characteristic observed in vitro and in situ. Model rate constants were obtained by minimizing the distance between model and experimental outcomes...
September 1, 2015: American Journal of Physiology. Renal Physiology
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