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Gayatri Padhy, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, Niroj Kumar Sethy
Padhy Gayatri, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, and Niroj Kumar Sethy. Plasma proteomics of Ladakhi natives reveal functional regulation between renin-angiotensin system and eNOS-cGMP pathway. High Alt Med Biol. 16:000-000, 2016.-Humans have been living in high altitudes for more than 25,000 years but the molecular pathways promoting survival and performance in these extreme environments are not well elucidated. In an attempt to understand human adaptation to high altitudes, we used two-dimensional gel electrophoresis combined with MALDI-TOF/TOF to identify plasma proteins and associated pathways of ethnic Ladakhi natives residing at 3520 m...
October 14, 2016: High Altitude Medicine & Biology
Kevin D Burns, Yuliya Lytvyn, Farid H Mahmud, Denis Daneman, Livia Deda, David B Dunger, John E Deanfield, R Neil Dalton, Yesmino Elia, Ronnie Har, Julie A D Van, Timothy J Bradley, Cameron Slorach, Wei Hui, Fengxia Xiao, Joseph Zimpelmann, Luc Mertens, Rahim Moineddin, Heather N Reich, Etienne B Sochett, James W Scholey, David Z I Cherney
AIMS: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess (1) levels of urinary RAAS components and (2) the association between RAAS components and HbA1c, urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and blood pressure in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). METHODS: Urinary angiotensinogen and ACE2 levels, activity of ACE and ACE2, blood pressure (BP), HbA1c, ACR and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)...
October 12, 2016: American Journal of Physiology. Renal Physiology
Tao-Cheng Wu, Chiu-Yang Lee, Shing-Jong Lin, Jaw-Wen Chen
BACKGROUND: The renin-angiotensin system (RAS) plays an important role in atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress increases and contributes to endothelial dysfunction and vascular inflammation. Renin exerts effects through a renin receptor causing an increase in the efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II) generation and action on cell surfaces. Ang II enhances proliferation and migration of vascular smooth muscle cells, indicating a direct involvement of the RAS in smooth muscle cell proliferation during neointimal formation...
September 2016: Acta Cardiol Sin
Mitsumasa Umesawa, Gen Kobashi
Hypertensive disorders in pregnancy (HDP) represent some of the most important problems faced by public health because HDP is a major cause of maternal and prenatal morbidity and mortality. Several epidemiological studies have been performed to determine the prevalence and risk factors of HDP as well as its subtypes. The prevalences of HDP, gestational hypertension and preeclampsia are 5.2-8.2%, 1.8-4.4% and 0.2-9.2%, respectively. Body mass index, anemia and lower education appear to be modifiable risk factors for HDP...
September 29, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Hudie Wei, Haiyan Cai, Jiawei Wu, Zhenquan Wei, Fei Zhang, Xin Huang, Lina Ma, Lingling Feng, Ruoxi Zhang, Yunjie Wang, Hermann Ragg, Ying Zheng, Aiwu Zhou
Lamprey angiotensinogen (l-ANT) is a hormone carrier in the regulation of blood pressure, but it is also a heparin-dependent thrombin inhibitor in lamprey blood coagulation system. The detailed mechanisms on how angiotensin is carried by l-ANT and how heparin binds l-ANT and mediates thrombin inhibition are unclear. Here we have solved the crystal structure of cleaved l-ANT at 2.7 angstrom resolution and characterized its properties in heparin binding and protease inhibition. The structure reveals that l-ANT has a conserved serpin fold with a labile N-terminal angiotensin peptide and undergoes a typical stressed-to-relaxed conformational change when the reactive center loop is cleaved...
September 28, 2016: Journal of Biological Chemistry
Bosede B Afolabi, Olajumoke O Oladipo, Alani S Akanmu, Olalekan O Abudu, Olusoga A Sofola, Fiona Broughton Pipkin
BACKGROUND: Sickle cell disease (haemoglobin SS (HbSS)) mainly affects those of West African origin and is associated with hypervolaemia. Plasma volume rises by up to 50% in normal pregnancy but was previously found to be paradoxically contracted in late sickle cell pregnancy. The renin-angiotensin-aldosterone system is activated very early in human pregnancy to support the plasma volume expansion. We hypothesised that activation of the renin-angiotensin-aldosterone system would be blunted in pregnant women with sickle cell disease...
July 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Shun-Yang Cheng, Yu-Hsiang Chou, Fang-Ling Liao, Chi-Chun Lin, Fan-Chi Chang, Chia-Hao Liu, Tao-Min Huang, Chun-Fu Lai, Yu-Feng Lin, Vin-Cent Wu, Tzong-Shinn Chu, Ming-Shiou Wu, Shuei-Liong Lin
Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury...
September 28, 2016: Scientific Reports
Bancha Satirapoj, Kasemsan Aramsaowapak, Theerasak Tangwonglert, Ouppatham Supasyndh
Background. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. Methods. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured...
2016: Journal of Diabetes Research
Stephen Harrap, Katrina Scurrah, Angela Lamantia, Justine Ellis
OBJECTIVE: Genes encoding key elements of the renin-angiotensin-aldosterone system (RAAS) cascade have been previously but inconsistently associated with blood pressure. Sex-dependency might be important here and functional genetic polymorphisms might exhibit epistatic effects. DESIGN AND METHOD: We assessed variation in the genes encoding renin (REN), angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1) and aldosterone synthase (CYP11B2)...
September 2016: Journal of Hypertension
Steven Hunt, Paul Hopkins, Nazeem Nanjee, Karen Schwander, Donald Kohan, D C Rao, Gordon Williams
OBJECTIVE: Identify the earliest hormonal, electrolyte and gene expression responses to a saline infusion before compensatory mechanisms are activated and relate these responses to delayed sodium excretion. DESIGN AND METHOD: 233 normotensive subjects with a strong positive family history of hypertension, ages 21-65, were studied on a low sodium diet before, during and after a 2-hour, 2-liter saline infusion. Plasma and urine hormones of the renin-angiotensin-aldosterone, catecholamine, uric acid, kallikrein, and cortisol pathways, microalbumin, and urine and plasma electrolytes were measured...
September 2016: Journal of Hypertension
James Scholey
The classical view of the RAS is a linear signaling pathway beginning with the conversion of angiotensinogen to ANG I by renin, an enzyme secreted by the kidney. ANG I is converted to ANG II by angiotensin converting enzyme (ACE) ANG II binds to the G-protein coupled angiotensin II receptor type 1. The RAS is a circulating system but we now know that the RAS is also locally expressed in a number of tissues, including the kidneys and the heart. ANG II exerts adverse hemodynamic and non-hemodynamic effects on renal cells...
September 2016: Journal of Hypertension
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
Juan Wang, Hiroyuki Kobori, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Previous studies have shown that angiotensinogen (AGT) synthesis is enhanced by high glucose (HG) in rat renal proximal tubular cells. We aimed to investigate the glucose-responsive elements within human AGT (hAGT) promoter in human immortalized proximal tubular HK-2 cells. DESIGN AND METHOD: HK-2 cells were treated with normal glucose (NG: 5.5 mmol/L) and high glucose (HG: 15 mmol/L). Human AGT promoter region was cloned from -4358 to +122. Consecutive 5'-end deletion mutant constructs and different site-direct mutagenesis products were transfected into HK-2, followed by promoter activity measurement by dual luciferase assay...
September 2016: Journal of Hypertension
Risa Ramadhiani, Muhammad Saifur Rohman, Nashi Widodo, Valerinna Y S Putri, Mifetika Lukitasari, Jayarani F Putri, Didik H Utomo
OBJECTIVE: To investigate whether the angiotensinogen (AGT) G-217A polymorphism affects blood pressure response of telmisartan and valsartan in hypertensive patients. DESIGN AND METHOD: A total of 46 primary hypertensive patients, 23 patients received telmisartan 80 mg and 23 patients received valsartan 160 mg, were observed and followed up for 4 months. The AGT G-217A polymorphism was determined by PCR-RFLP and direct sequencing method. Blood pressure response was measured daytime (6 am - 10 pm), night-time (10 pm - 6 am), and 24 hours using twenty-four hours ambulatory blood pressure monitoring (ABPM)...
September 2016: Journal of Hypertension
Akira Nishiyama
The renin-angiotensin system (RAS) plays a critical role in the regulation of blood pressure and body fluid homeostasis. In addition to its physiological roles, angiotensin II (AngII) induces inflammation, cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, all of which contribute to renal tissue injuries. In the kidney, all of the RAS components are present and intrarenal AngII is formed by independent multiple mechanisms...
September 2016: Journal of Hypertension
Hisashi Kai
There is increasing evidence that fibro-inflammatory changes play a role in variety of cardiovascular diseases. We created new rat models to investigate the role of fibro-inflammatory changes in the pathophysiology of systolic and diastolic dysfunction in hypertensive heart. (1) a model of a blood pressure (BP) surge was created by performing abdominal aortic constriction in Wistar-Kyoto rats. Aortic constriction rapidly increased BP and the high BP levels sustained. A BP surge transiently induced MCP-1 and TGF-beta induction, angiotensin converting enzyme activation, and macrophage infiltration, followed by left ventricular (LV) hypertrophy and perivascular reactive fibrosis...
September 2016: Journal of Hypertension
Shiao-Ying Chang, Chao-Sheng Lo, Xin-Ping Zhao, Min-Chun Liao, Isabelle Chenier, Richard Bouley, Julie R Ingelfinger, John Sd Chan, Shao-Ling Zhang
INTRODUCTION: We aimed to examine the regulation of aquaporin 1 expression in an angiotensinogen transgenic mouse model, focusing on underlying mechanisms. METHODS: Male transgenic mice overexpressing rat angiotensinogen in their renal proximal tubular cells (RPTCs) and rat immortalised RPTCs stably transfected with rat angiotensinogen cDNA were used. RESULTS: Angiotensinogen-transgenic mice developed hypertension and nephropathy, changes that were either partially or completely attenuated by treatment with losartan or dual renin-angiotensin system blockade (losartan and perindopril), respectively, while hydralazine prevented hypertension but not nephropathy...
July 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Caroline Gusson Shimoura, Gisele Silvério Lincevicius, Erika Emy Nishi, Adriana Castello Costa Girardi, Karin Argenti Simon, Cassia de Toledo Bergamaschi, Ruy Ribeiro Campos
BACKGROUND: Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin-angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance. AIM: The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system...
September 14, 2016: American Journal of Hypertension
Cornelis Kluft, Yvette Zimmerman, Marie Mawet, Christine Klipping, Ingrid J M Duijkers, Jacoline Neuteboom, Jean-Michel Foidart, Herjan Coelingh Bennink
OBJECTIVE: The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers. STUDY DESIGN: Combinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15-18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle...
September 1, 2016: Contraception
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