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Salt sensitive hypertension

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https://www.readbyqxmd.com/read/28069662/endoplasmic-reticulum-stress-inhibition-limits-the-progression-of-chronic-kidney-disease-in-the-dahl-salt-sensitive-rat
#1
Victoria Yum, Rachel E Carlisle, Chao Lu, Elise Brimble, Jasmine Chahal, Chandak Upagupta, Kjetil Ask, Jeffrey G Dickhout
Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28067240/cd8-t-cells-stimulate-na-cl-co-transporter-ncc-in-distal-convoluted-tubules-leading-to-salt-sensitive-hypertension
#2
Yunmeng Liu, Tonya M Rafferty, Sung W Rhee, Jessica S Webber, Li Song, Benjamin Ko, Robert S Hoover, Beixiang He, Shengyu Mu
Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28062568/renal-collectrin-protects-against-salt-sensitive-hypertension-and-is-downregulated-by-angiotensin-ii
#3
Pei-Lun Chu, Joseph C Gigliotti, Sylvia Cechova, Gabor Bodonyi-Kovacs, Fang Chan, Donna Lee Ralph, Nancy Howell, Kambiz Kalantari, Alexander L Klibanov, Robert M Carey, Alicia A McDonough, Thu H Le
Collectrin, encoded by the Tmem27 gene, is a transmembrane glycoprotein with approximately 50% homology with angiotensin converting enzyme 2, but without a catalytic domain. Collectrin is most abundantly expressed in the kidney proximal tubule and collecting duct epithelia, where it has an important role in amino acid transport. Collectrin is also expressed in endothelial cells throughout the vasculature, where it regulates L-arginine uptake. We previously reported that global deletion of collectrin leads to endothelial dysfunction, augmented salt sensitivity, and hypertension...
January 6, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28062494/cellular-repressor-of-e1a-stimulated-genes-is-a-critical-determinant-of-vascular-remodeling-in-response-to-angiotensin-ii
#4
Li Yang, Liu Yanxia, Tian Xiaoxiang, Zhang Yan, Song Haixu, Liu Meili, Zhang Xiaolin, Liu Haiwei, Zhang Jian, Zhang Quanyu, Liu Dan, Peng Chengfei, Yan Chenghui, Han Yaling
OBJECTIVE: Cellular repressor of E1A-stimulated genes (CREG) is a lysosomal glycoprotein implicated in maintaining vascular homeostasis. Here, we have hypothesized that CREG is a critical target of intervention for the prevention of hypertensive vascular remodeling. APPROACH AND RESULTS: CREG gene expression was significantly decreased accompanied by an upregulated expression of angiotensin II (Ang II) in remodeled vascular tissues of high salt-induced Dahl salt-sensitive rats and Ang II-induced mice...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28052878/high-frequency-of-variants-of-candidate-genes-in-black-africans-with-low-renin-resistant-hypertension
#5
Erika S Jones, J David Spence, Adam D Mcintyre, Justus Nondi, Kennedy Gogo, Adeseye Akintunde, Daniel G Hackam, Brian L Rayner
OBJECTIVES: Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important. METHODS: Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequenced if the aldosterone level was low (Liddle phenotype)...
January 4, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#6
Katharina Ilse Blankenstein, Aljona Borschewski, Robert Labes, Alexander Paliege, Christin Boldt, James A McCormick, David H Ellison, Michael Bader, Sebastian Bachmann, Kerim Mutig
Calcineurin dephosphorylates NFAT transcription factors, thereby facilitating T-cell mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation, but may cause side effects including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003189/involvement-of-enac-in-the-development-of-salt-sensitive-hypertension
#7
Tengis S Pavlov, Alexander Staruschenko
Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27993957/activation-of-renal-pro-renin-receptor-contributes-to-high-fructose-induced-salt-sensitivity
#8
Chuanming Xu, Aihua Lu, Xiaohan Lu, Linlin Zhang, Hui Fang, Li Zhou, Tianxin Yang
A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. High-fructose intake also upregulated renal mRNA and protein expression of sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, as well as in vivo Na/K/2Cl cotransporter activity, all of which were nearly completely blocked by a PRR decoy inhibitor PRO20 or allopurinol treatment...
December 19, 2016: Hypertension
https://www.readbyqxmd.com/read/27988209/renal-tubular-angiotensin-converting-enzyme-is%C3%A2-responsible-for-nitro-l-arginine-methyl-ester%C3%A2-l-name-induced-salt-sensitivity
#9
Jorge F Giani, Masahiro Eriguchi, Ellen A Bernstein, Makoto Katsumata, Xiao Z Shen, Liang Li, Alicia A McDonough, Sebastien Fuchs, Kenneth E Bernstein, Romer A Gonzalez-Villalobos
Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27922176/dipeptidyl-peptidase-4-inhibitor-sitagliptin-reduces-inflammation-fibrosis-and-preserves-diastolic-function-in-a-rat-model-of-heart-failure-with-preserved-ejection-fraction
#10
Grazia Esposito, Donato Cappetta, Rosa Russo, Alessia Rivellino, Loreta Pia Ciuffreda, Fiorentina Roviezzo, Elena Piegari, L Liberato Berrino, Francesco Rossi, Antonella De Angelis, Konrad Urbanek
BACKGROUND AND PURPOSE: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome driven by co-morbidities and its pathophysiology is poorly understood. Several studies suggesting that dipeptidyl peptidase 4 (DPP4) might be involved in the pathophysiology of heart failure prompted experimental and clinical investigations of DPP4 inhibitors on cardiovascular system. The aim of our study was to determine whether DPP4 inhibitor sitagliptin (SITA) affects the progression of HFpEF independently from the effects on glycaemia...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27920129/chronic-inhibition-of-renal-outer-medullary-potassium-channel-not-only-prevented-but-also-reversed-development-of-hypertension-and-end-organ-damage-in-dahl-salt-sensitive-rats
#11
Xiaoyan Zhou, Michael J Forrest, Wanda Sharif-Rodriguez, Gail Forrest, Daphne Szeto, Olga Urosevic-Price, Yonghua Zhu, Andra S Stevenson, Yuchen Zhou, Sloan Stribling, Maya Dajee, Shawn P Walsh, Alexander Pasternak, Kathleen A Sullivan
The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc...
December 5, 2016: Hypertension
https://www.readbyqxmd.com/read/27906747/update-on-angiotensin-at2-receptors
#12
Robert M Carey
PURPOSE OF REVIEW: This review updates major new findings and concepts introduced during the past year on the role of angiotensin II (Ang II) subtype 2 receptors (AT2Rs) in the control of blood pressure and renal function. RECENT FINDINGS: AT2R activation prevents sodium (Na) retention and lowers blood pressure in the Ang II infusion model of experimental hypertension and prevents salt-sensitive hypertension in the obese Zucker rat model of obesity and the metabolic syndrome...
November 30, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27903222/sustained-elabela-gene-therapy-in-high-salt-induced-hypertensive-rats
#13
Claire A Schreiber, Sara J Holditch, Alex Generous, Yasuhiro Ikeda
BACKGROUND: Elabela (ELA) is a recently identified apelin receptor agonist essential for cardiac development, but its biology and therapeutic potential are unclear. In humans ELA transcripts are detected in embryonic stem cells, induced pluripotent stem cells, kidney, heart and blood vessels. ELA through the apelin receptor promotes angiogenesis in vitro, relaxes murine aortic blood vessels and attenuates high blood pressure in vivo. The apelin receptor when bound to its original ligand, apelin, exerts peripheral vasodilatory and positive inotropic effects, conferring cardioprotection in vivo...
November 21, 2016: Current Gene Therapy
https://www.readbyqxmd.com/read/27895193/organum-vasculosum-of-the-lamina-terminalis-detects-nacl-to-elevate-sympathetic-nerve-activity-and-blood-pressure
#14
Brian J Kinsman, Sarah S Simmonds, Kirsteen N Browning, Sean D Stocker
High-salt diet elevates NaCl concentrations in the cerebrospinal fluid to increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. The organum vasculosum of the lamina terminalis (OVLT) resides along the rostral wall of the third ventricle, lacks a complete blood-brain barrier, and plays a pivotal role in body fluid homeostasis. Therefore, the present study used a multifaceted approach to examine whether OVLT neurons of Sprague-Dawley rats are intrinsically sensitive to changes in extracellular NaCl concentrations and mediate the sympathoexcitatory responses to central NaCl loading...
January 2017: Hypertension
https://www.readbyqxmd.com/read/27884238/the-pressure-of-aging
#15
REVIEW
Majd AlGhatrif, Mingyi Wang, Olga V Fedorova, Alexei Y Bagrov, Edward G Lakatta
Significant hemodynamic changes ensue with aging, leading to an ever-growing epidemic of hypertension. Alterations in central arterial properties play a major role in these hemodynamic changes. These alterations are characterized by an initial decline in aortic distensibility and an increase of diastolic blood pressure, followed by a sharp increase in pulse wave velocity (PWV), and an increase in pulse pressure (PP) beyond the sixth decade. However, the trajectories of PWV and PP diverge with advancing age...
January 2017: Medical Clinics of North America
https://www.readbyqxmd.com/read/27862163/the-effects-of-high-sodium-intake-on-systemic-blood-pressure-and-vascular-responses-in-spontaneously-diabetic-wbn-kob-lepr-fa-fa-rats
#16
Yoshiichi Takagi, Haruno Kadowaki, Ikumi Kobayashi, Kaoru Ito, Katsuaki Ito, Mitsuyuki Shirai, Fumitoshi Asai
The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high-salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob-Lepr(fa/fa) (WBKDF) rats, a new spontaneous animal model of T2DM. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (0.26%, NS) diet or high-sodium (8%, HS) diet for 14 weeks: 1) Wistar rats on NS diet (Wistar-NS); 2) Wistar rats on HS diet (Wistar-HS); 3) WBKDF rats on NS diet (WBKDF-NS); 4) WBKDF rats on HS diets (WBKDF-HS)...
November 15, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27849566/effects-of-sacubitril-valsartan-lcz696-on-natriuresis-diuresis-blood-pressures-and-nt-probnp-in-salt-sensitive-hypertension
#17
Tzung-Dau Wang, Ru-San Tan, Hae-Young Lee, Sang-Hyun Ihm, Moo-Yong Rhee, Brian Tomlinson, Parasar Pal, Fan Yang, Elizabeth Hirschhorn, Margaret F Prescott, Markus Hinder, Thomas H Langenickel
: Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet...
January 2017: Hypertension
https://www.readbyqxmd.com/read/27815929/challenges-in-the-management-of-hypertension-in-older-populations
#18
Lisa Pont, Tariq Alhawassi
The prevalence of hypertension increases with age making it a significant health concern for older persons. Aging involves a range of physiological changes such as increases in arterial stiffness, widening pulse pressure, changes in renin and aldosterone levels, decreases in renal salt excretion, declining in renal function, changes in the autonomic nervous system sensitivity and function and changes to endothelial function all of which may not only affect blood pressure but may also affect individual response to pharmacotherapy used to manage hypertension and prevent end organ damage and other complications associated with poor blood pressure control...
November 5, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27815594/wnk-signalling-pathways-in-blood-pressure-regulation
#19
REVIEW
Meena Murthy, Thimo Kurz, Kevin M O'Shaughnessy
Hypertension (high blood pressure) is a major public health problem affecting more than a billion people worldwide with complications, including stroke, heart failure and kidney failure. The regulation of blood pressure is multifactorial reflecting genetic susceptibility, in utero environment and external factors such as obesity and salt intake. In keeping with Arthur Guyton's hypothesis, the kidney plays a key role in blood pressure control and data from clinical studies; physiology and genetics have shown that hypertension is driven a failure of the kidney to excrete excess salt at normal levels of blood pressure...
November 4, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27814606/regulation-and-function-of-renal-medullary-cyclooxygenase-2-during-high-salt-loading
#20
Tianxin Yang, Mi Liu
Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE2 is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE2 excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1 alpha (HIF-1 alpha)...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
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