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Salt sensitive hypertension

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https://www.readbyqxmd.com/read/28635325/effect-of-salt-loading-on-baroreflex-sensitivity-in-reduced-renal-mass-hypertension
#1
Besim Özaykan, Eylem Taskin, Ali Magemizoğlu
BACKGROUND: High dietary salt, as well as renal mass reduction, is known to decrease baroreflex sensitivity in rats. However, the effect of high salt intake on baroreflex sensitivity is unknown in reduced renal mass (RRM) hypertension; therefore, the aim of this study was to investigate the effects of salt loading on arterial baroreflex sensitivity and mean arterial pressure (MAP) in RRM hypertension. METHODS: Both RRM and sham-operated control (SO) rats were loaded with 0...
June 21, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28628530/effects-of-salt-loading-and-potassium-supplement-on-the-circadian-blood-pressure-profile-in-salt-sensitive-chinese-patients
#2
Tong-Shuai Guo, Yi Dai, Ke-Yu Ren, Jian-Jun Mu, Jie Ren, Dan Wang, Yang Wang, Chao Chu, Yan Li, Zu-Yi Yuan
BACKGROUND AND OBJECTIVE: Salt-sensitive (SS) patients more frequently showed a nondipper blood pressure pattern and were associated with more serious target organ damage than non-SS patients. We aimed to investigate whether potassium supplement can improve the blunted nocturnal blood pressure fall in SS patients exposed to a high-salt diet. PATIENTS AND METHODS: Approximately 49 normotensive and mildly hypertensive Chinese patients received a study protocol of a 3 days of baseline examination, 7 days of a low-salt diet (3 g NaCl/day), 7 days of a high-salt diet (18 g NaCl/day), and 7 days of a high-salt diet with a potassium supplement (18 g NaCl and 4...
June 16, 2017: Blood Pressure Monitoring
https://www.readbyqxmd.com/read/28613240/an-isoform-of-nedd4-2-plays-a-pivotal-role-in-electrophysiological-cardiac-abnormalities
#3
Shintaro Minegishi, Tomoaki Ishigami, Hisho Kawamura, Tabito Kino, Lin Chen, Rie Nakashima-Sasaki, Hiroshi Doi, Kengo Azushima, Hiromichi Wakui, Yumi Chiba, Kouichi Tamura
We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr)...
June 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28604611/eplerenone-resistant-salt-sensitive-hypertension-in-nedd4-2-c2-ko-mice
#4
Tabito Kino, Tomoaki Ishigami, Tsumugi Murata, Hiroshi Doi, Rie Nakashima-Sasaki, Lin Chen, Michiko Sugiyama, Kengo Azushima, Hiromichi Wakui, Shintaro Minegishi, Kouichi Tamura
The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake...
June 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28588673/modulatory-effects-of-hydrochlorothiazide-and-triamterene-on-resistant-hypertension-patients
#5
Haibin Gong, Yun Li, Cheng Zheng, Tian-Tian Du, Bing-Quan Luo, Min Pang
The present study explored the modulatory potential of hydrochlorothiazide and triamterene on resistant hypertension patients. The mechanistic information for resistant hypertension was explored by studying the pressure-natriuresis curves between the salt sensitive population and non-salt sensitive population. A cohort of 23 patients with non-hypertension (NH) (13 males and 10 females; aged from 23 to 62 years), 26 patients with controlled hypertension (CH) (14 males and 12 females; aged from 19 to 72 years) and 23 patients with resistant hypertension (RH) (13 males and 10 females; aged from 19 to 76 years) were selected...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#6
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
June 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28566208/development-of-wnk-signaling-inhibitors-as-a-new-class-of-antihypertensive-drugs
#7
Mari Ishigami-Yuasa, Yuko Watanabe, Takayasu Mori, Hiroyuki Masuno, Shinya Fujii, Eriko Kikuchi, Shinichi Uchida, Hiroyuki Kagechika
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia and hypertension despite a normal glomerular filtration rate. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension. Thus, inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for a new class of antihypertensive drugs. In this study, we developed novel inhibitors of this signal cascade from the 9-aminoacridine lead compound 1, one of the hit compounds obtained by screening our chemical library for WNK-SPAK binding inhibitors...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28560105/the-metabolic-profile-of-a-rat-model-of-chronic-kidney-disease
#8
Yohei Tanada, Junji Okuda, Takao Kato, Eri Minamino-Muta, Ichijiro Murata, Tomoyoshi Soga, Tetsuo Shioi, Takeshi Kimura
BACKGROUND: The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. METHODS: We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney...
2017: PeerJ
https://www.readbyqxmd.com/read/28556624/a-quantitative-systems-physiology-model-of-renal-function-and-blood-pressure-regulation-application-in-salt-sensitive-hypertension
#9
K M Hallow, Y Gebremichael
Salt-sensitivity (SS) refers to changes in blood pressure in response to changes in sodium intake. SS individuals are at greater risk for developing kidney disease, and also respond differently to antihypertensive therapies compared to salt-resistant (SR) individuals. In this study we used a systems pharmacology model of renal function (presented in a companion article) to evaluate the ability of proposed mechanisms to produce salt-sensitivity. The model reproduced previously published data on renal functional changes in response to salt-intake, and also predicted that glomerular pressure, a variable that is not easily evaluated clinically but is a key factor in renal injury, increases with salt intake in SS hypertension...
May 27, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28548387/a-quantitative-systems-physiology-model-of-renal-function-and-blood-pressure-regulation-model-description
#10
K M Hallow, Y Gebremichael
Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses...
May 26, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28538181/malate-and-aspartate-increase-l-arginine-and-nitric-oxide-and-attenuate-hypertension
#11
Entai Hou, Na Sun, Fuchang Zhang, Chenyang Zhao, Kristie Usa, Mingyu Liang, Zhongmin Tian
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28530328/-the-israeli-rat-genome-center
#12
REVIEW
Yoram Yagil, Chana Yagil
The Israeli Rat Genome Center, which is located at the Barzilai Medical Center Campus of the Faculty of Health Sciences of the Ben-Gurion University of the Negev in Ashkelon, was established to provide a repository of unique genetic strains of rats that were created in Israel and that simulate complex diseases. The Center incorporates models of: salt-sensitive hypertension (SBN/y and SBH/y rats), type 2 diabetes (CDr and CDs rats), combined hypertension and diabetes (CRDH) and additional genetic strains (transgenics, consomics, congenics)...
August 2016: Harefuah
https://www.readbyqxmd.com/read/28501304/speculations-on-salt-and-the-genesis-of-arterial-hypertension
#13
REVIEW
Jens Titze, Friedrich C Luft
Blood pressure salt sensitivity and salt resistance are mechanistically imperfectly explained. A prescient systems medicine approach by Guyton and colleagues-more than 50 years ago-suggested how salt intake might influence blood pressure. They proposed that a high-salt diet engenders sodium accumulation, volume expansion, cardiac output adjustments, and then autoregulation for flow maintenance. The autoregulation in all vascular beds increases systemic vascular resistance, causing the kidneys to excrete more salt and water, thus reducing systems to normal and minimizing any changes in blood pressure...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28482823/t-cells-contribute-to-hypertension-but-not-to-renal-injury-in-mice-with-subtotal-nephrectomy
#14
Nynke R Oosterhuis, Diana A Papazova, Hendrik Gremmels, Jaap A Joles, Marianne C Verhaar
BACKGROUND: The pathological condition of chronic kidney disease may not be adequately recapitulated in immunocompromised mice due to the lack of T-cells, which are important for the development of hypertension and renal injury. We studied the role of the immune system in relation to salt-sensitive hypertension and renal injury in mice with subtotal nephrectomy (SNX). METHODS: Wild-type immunocompetent (WT) and Foxn1(nu/nu) athymic immunodeficient (AT) CD-1 mice underwent SNX to induce renal injury after which they received standard chow or a high salt diet (HSD)...
May 8, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28473772/lack-of-effects-of-metformin-and-aicar-chronic-infusion-on-the-development-of-hypertension-in-dahl-salt-sensitive-rats
#15
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Hui Li, Oleg Palygin, Nuria M Pastor-Soler, Kenneth R Hallows, Alexander Staruschenko
In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446801/genetic-susceptibility-to-salt-sensitive-hypertension-in-a-han-chinese-population-a-validation-study-of-candidate-genes
#16
Zheng Liu, Han Qi, Bin Liu, Kuo Liu, Jingjing Wu, Han Cao, Jie Zhang, Yuxiang Yan, Yan He, Ling Zhang
Salt-sensitive hypertension is a complex disease associated with genetic factors. This study aimed to identify the association between 29 candidate single-nucleotide polymorphisms and salt-sensitive hypertension in a Han Chinese population. Sixty-three participants with salt-sensitive hypertension and 279 controls with salt-resistant hypertension were recruited. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to detect blood pressure salt sensitivity. Lifestyle risk factors were obtained via a questionnaire...
April 27, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28445253/micro-rna-screening-and-prediction-model-construction-for-diagnosis-of-salt-sensitive-essential-hypertension
#17
Han Qi, Zheng Liu, Bin Liu, Han Cao, Weiping Sun, Yuxiang Yan, Ling Zhang
Commonly used tests for diagnosis of salt-sensitive hypertension (SSH) are complex and time-consuming, so new methods are required. Many studies have demonstrated roles for miRNAs in hypertension; however, the diagnostic value of miRNAs has yet to be determined for human SSH. In this study, we examined miRNA expression profiles by initial high-throughput miRNA sequencing of samples from patients with salt-sensitive and salt-resistant hypertension (SSH and SRH, respectively; n = 6, both groups), followed by validation by quantitative real-time polymerase chain reaction (qRT-PCR) in a larger cohort (n = 91)...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28445205/inhibition-of-microrna-429-in-the-renal-medulla-increased-salt-sensitivity-of-blood-pressure-in-sprague-dawley-rats
#18
Qing Zhu, Junping Hu, Lei Wang, Weili Wang, Zhengchao Wang, Pin-Lan Li, Krishna M Boini, Ningjun Li
BACKGROUND: We have previously shown that high salt intake suppresses the expression of prolyl hydroxylase domain-containing protein 2 (PHD2), an enzyme promoting the degradation of hypoxia-inducible factor (HIF)-1α, and increases HIF-1α along with its target genes in the renal medulla, which promotes sodium excretion and regulate salt sensitivity of blood pressure. However, it remains unknown how high salt inhibits the expression of PHD2. METHOD AND RESULTS: The current study first revealed that high-salt-induced PHD2 inhibition was due to the enhanced decay of mRNA...
April 25, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28430843/carotid-body-denervation-markedly-improves-survival-in-rats-with-hypertensive-heart-failure
#19
Kana Fujii, Keita Saku, Takuya Kishi, Yasuhiro Oga, Takeshi Tohyama, Takuya Nishikawa, Takafumi Sakamoto, Masataka Ikeda, Tomomi Ide, Hiroyuki Tsutsui, Kenji Sunagawa
BACKGROUND: Hypertension is a major cause of heart failure. Excessive sympathoexcitation in patients with heart failure leads to poor prognosis. Since carotid body denervation (CBD) has been shown to reduce sympathetic nerve activity in animal models of hypertension and heart failure, we examined if bilateral CBD attenuates the progression of hypertensive heart failure and improves survival. METHODS: We randomly allocated Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n = 50) groups, and conducted CBD or SHAM at 7 weeks of age...
April 19, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28430812/nacl-cotransporter-abundance-in-urinary-vesicles-is-increased-by-calcineurin-inhibitors-and-predicts-thiazide-sensitivity
#20
Omar A Z Tutakhel, Arthur D Moes, Marco A Valdez-Flores, Marleen L A Kortenoeven, Mathijs V D Vrie, Sabina Jeleń, Robert A Fenton, Robert Zietse, Joost G J Hoenderop, Ewout J Hoorn, Luuk Hilbrands, René J M Bindels
Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics...
2017: PloS One
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