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Sample records for expression normalises hypertension

  1. Normalisation genes for expression analyses in the brown alga model Ectocarpus siliculosus

    PubMed Central

    Le Bail, Aude; Dittami, Simon M; de Franco, Pierre-Olivier; Rousvoal, Sylvie; Cock, Mark J; Tonon, Thierry; Charrier, Bénédicte

    2008-01-01

    Background Brown algae are plant multi-cellular organisms occupying most of the world coasts and are essential actors in the constitution of ecological niches at the shoreline. Ectocarpus siliculosus is an emerging model for brown algal research. Its genome has been sequenced, and several tools are being developed to perform analyses at different levels of cell organization, including transcriptomic expression analyses. Several topics, including physiological responses to osmotic stress and to exposure to contaminants and solvents are being studied in order to better understand the adaptive capacity of brown algae to pollution and environmental changes. A series of genes that can be used to normalise expression analyses is required for these studies. Results We monitored the expression of 13 genes under 21 different culture conditions. These included genes encoding proteins and factors involved in protein translation (ribosomal protein 26S, EF1alpha, IF2A, IF4E) and protein degradation (ubiquitin, ubiquitin conjugating enzyme) or folding (cyclophilin), and proteins involved in both the structure of the cytoskeleton (tubulin alpha, actin, actin-related proteins) and its trafficking function (dynein), as well as a protein implicated in carbon metabolism (glucose 6-phosphate dehydrogenase). The stability of their expression level was assessed using the Ct range, and by applying both the geNorm and the Normfinder principles of calculation. Conclusion Comparisons of the data obtained with the three methods of calculation indicated that EF1alpha (EF1a) was the best reference gene for normalisation. The normalisation factor should be calculated with at least two genes, alpha tubulin, ubiquitin-conjugating enzyme or actin-related proteins being good partners of EF1a. Our results exclude actin as a good normalisation gene, and, in this, are in agreement with previous studies in other organisms. PMID:18710525

  2. Aberrant Liver Insulin Receptor Isoform A Expression Normalises with Remission of Type 2 Diabetes after Gastric Bypass Surgery

    PubMed Central

    Besic, Vinko; Shi, Hongjun; Stubbs, Richard S.; Hayes, Mark T.

    2015-01-01

    Type 2 diabetes mellitus (T2DM) results from a combination of progressive insulin resistance and loss of pancreatic beta cell function and/or mass. Insulin signalling occurs through the insulin receptor, (INSR) which is alternatively spliced into two isoforms: INSRA (-exon 11) and INSRB (+exon 11). Because the INSR isoforms have different functional characteristics, their relative expression ratio has been implicated in the pathogenesis of insulin resistance and T2DM. We studied levels of INSR isoform mRNA in liver samples taken from 46 individuals with or without T2DM at Roux-en-Y (RYGB) surgery, and on average 17 (± 5.6) months later in 16 of the same individuals (8 diabetic and non-diabetic patients). INSRA or INSRB was also overexpressed in HepG2 cells to ascertain their effect on AKT phosphorylation and PCK1 expression as markers of insulin-mediated metabolic signalling. We found the INSRB:A isoform ratio was reduced in individuals with T2DM in comparison to those with normal glucose tolerance and normalised with remission of diabetes. The INSRB:A ratio increased due to a reduction in the alternatively spliced INSRA isoform following remission of diabetes. Overexpressing INSRA isoform in HepG2 hepatoma cells reduced inhibition of PCK1 transcription and did not increase AKT phosphorylation in response to insulin load compared to the effect of overexpressing the B isoform. Data presented here revitalizes the role of the INSR isoforms in the pathogenesis of T2DM, and suggests that an abrogated INSRB:A ratio that favours the INSRA isoform may negatively impact insulin-mediated metabolic signalling. PMID:25742416

  3. Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L.)

    PubMed Central

    Erskine, William; Nelson, Matthew N.

    2016-01-01

    Quantitative Reverse Transcription PCR (qRT-PCR) is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop) using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC), Helicase (HEL), and Polypyrimidine tract-binding protein (PTB)] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots) encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other potentially more

  4. Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L.).

    PubMed

    Taylor, Candy M; Jost, Ricarda; Erskine, William; Nelson, Matthew N

    2016-01-01

    Quantitative Reverse Transcription PCR (qRT-PCR) is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop) using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC), Helicase (HEL), and Polypyrimidine tract-binding protein (PTB)] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots) encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other potentially more

  5. Response to "The Normalised Child"

    ERIC Educational Resources Information Center

    Chisnall, Nicola

    2005-01-01

    Grebennikov has chosen to present to the contemporary gaze, the so-called "absolute" concepts of Maria Montessori regarding normalisation and deviation in childhood. Grebennikov has focussed on the issue of challenging behaviour and the "deviations" identified by Montessori 100 years ago. His discursive treatment of the topic complicates…

  6. Hypertension.

    PubMed

    Oparil, S; Calhoun, D A

    1989-03-01

    An estimated 58 million Americans are at increased risk of morbidity and premature death due to high blood pressure (BP) and require some type of therapy or systematic monitoring. This article focuses on recent advances in our understanding of the pathogenesis of hypertension, new approaches to the diagnosis and treatment of secondary hypertension, and current views of the most appropriate nonpharmacologic and pharmacologic therapy for essential hypertension. In view of the extremely high prevalence of the disorder, emphasis is placed on efficient and cost-effective strategies for diagnosing and managing the hypertensive patient. Recent evidence indicates that nonpharmacologic therapy, including dietary potassium and calcium supplements, reduction of salt intake, weight loss for the obese patient, regular exercise, a diet high in fiber and low in cholesterol and saturated fats, smoking cessation, and moderation of alcohol consumption produces significant sustained reductions in BP while reducing overall cardiovascular risk. Accordingly, nonpharmacologic antihypertensive therapy should be included in the treatment of all hypertensive patients. In persons with mild hypertension, nonpharmacologic approaches may adequately reduce BP, thereby avoiding the expense and potential side effects of drug therapy. In patients with more severe hypertension, nonpharmacologic therapy, used in conjunction with pharmacologic therapy, can reduce the dosage of antihypertensive medications necessary for BP control. Patients treated with nonpharmacologic therapy only should be followed closely, and if BP control is not satisfactory, drug therapy should be added. The large number of drugs available for use in hypertension treatment, coupled with our rapidly expanding knowledge of the pathophysiology of hypertension and of the adverse effects of these drugs in individual patient groups, make it possible to individualize antihypertensive treatment. When used as monotherapy, most agents

  7. Hypertension.

    PubMed

    Poulter, Neil R; Prabhakaran, Dorairaj; Caulfield, Mark

    2015-08-22

    Raised blood pressure is the biggest single contributor to the global burden of disease and to global mortality. The numbers of people affected and the prevalence of high blood pressure worldwide are expected to increase over the next decade. Preventive strategies are therefore urgently needed, especially in less developed countries, and management of hypertension must be optimised. Genetic advances in some rare causes of hypertension have been made lately, but the aggregate effect on blood pressure of all the genetic loci identified to date is small. Hence, intervention on key environmental determinants and effective implementation of trial-based therapies are needed. Three-drug combinations can control hypertension in about 90% of patients but only if resources allow identification of patients and drug delivery is affordable. Furthermore, assessment of optimal drug therapy for each ethnic group is needed. PMID:25832858

  8. Developmental expression of ACE2 in the SHR kidney: a role in hypertension?

    PubMed

    Tikellis, C; Cooper, M E; Bialkowski, K; Johnston, C I; Burns, W C; Lew, R A; Smith, A I; Thomas, M C

    2006-07-01

    The abnormal development of the intrarenal renin-angiotensin system (RAS) is thought contribute to adult-onset hypertension in the spontaneously hypertensive rat (SHR). Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with complementary actions to that of ACE. Recent studies have shown that ACE2 expression is reduced in the adult SHR. However, its regulation in pre-hypertensive animals is unknown. In this study, we examine the developmental expression of ACE2 in the rodent kidney and its temporal expression, as it relates to the development of hypertension in the SHR model. Kidneys from SHR and normotensive Wistar Kyoto (WKY) rats (n=8-12/group) at birth, 6 weeks of age, and adulthood (80 days) were examined. Gene expression and activity of ACE2 were determined by real-time reverse transcription-polymerase chain reaction and quenched fluorescence assays, respectively. Renal expression was localized by in situ hybridization and immunohistochemistry. The expression and ACE2 activity are significantly increased in the SHR kidney at birth. With the onset of hypertension, the tubular expression of ACE2 falls in SHR compared to WKY and remains reduced in the adult SHR kidney. Glomerular expression is paradoxically increased in the SHR glomerulus. The overall developmental pattern of ACE2 expression in the SHR kidney is also modified, with declining expression over the course of renal development. The developmental pattern of ACE2 expression in the SHR kidney is altered before the onset of hypertension, consistent with the key role of the RAS in the pathogenesis of adult-onset hypertension. Further research is required to distinguish the contribution of these changes to the development and progression of hypertension in this model. PMID:16710353

  9. Normalisation: what it means in practice.

    PubMed

    Barr, O

    Much of the development in the area of learning disabilities has been the result of normalisation. However, the term lacks definition. This article will explore the available definitions and outline some key components to be considered when incorporating normalisation into service provision. PMID:7703654

  10. Mesenchymal Stromal Cells Expressing Heme Oxygenase-1 Reverse Pulmonary Hypertension

    PubMed Central

    Liang, Olin D.; Mitsialis, S. Alex; Chang, Mun Seog; Vergadi, Eleni; Lee, Changjin; Aslam, Muhammad; Fernandez-Gonzalez, Angeles; Liu, Xianlan; Baveja, Rajiv; Kourembanas, Stella

    2012-01-01

    Pulmonary arterial hypertension (PAH) remains a serious disease, and, while current treatments may prolong and improve quality of life, search for novel and effective therapies is warranted. Using genetically-modified mouse lines, we tested the ability of bone marrow-derived stromal cells (MSCs), to treat chronic hypoxia-induced PAH. Recipient mice were exposed for five weeks to normobaric hypoxia (8%–10% O2), MSC preparations were delivered through jugular vein injection and their effect on PAH was assessed after two additional weeks in hypoxia. Donor MSCs derived from wild-type (WT) mice or Heme Oxygenase-1 (HO-1) null mice (Hmox1KO) conferred partial protection from PAH when transplanted into WT or Hmox1KO recipients, whereas treatment with MSCs isolated from transgenic mice harboring a human HO-1 transgene under the control of surfactant protein C promoter (SHO1 line) reversed established disease in WT recipients. SH01-MSC treatment of Hmox1KO animals, which develop right ventricular (RV) infarction under prolonged hypoxia, resulted in normal RV systolic pressure, significant reduction of RV hypertrophy and prevention of RV infarction. Donor MSCs isolated from a bitransgenic mouse line with doxycycline-inducible, lung-specific expression of HO-1 exhibited similar therapeutic efficacy only upon doxycycline treatment of the recipients. In vitro experiments indicate that potential mechanisms of MSC action include modulation of hypoxia-induced lung inflammation and inhibition of smooth muscle cell proliferation. Cumulative, our results demonstrate that MSCs ameliorate chronic hypoxia – induced PAH and their efficacy is highly augmented by lung-specific HO-1 expression in the transplanted cells, suggesting an interplay between HO-1 dependent and HO-1 independent protective pathways. PMID:20957739

  11. Nestin-expressing vascular wall cells drive development of pulmonary hypertension.

    PubMed

    Saboor, Farhan; Reckmann, Ansgar N; Tomczyk, Claudia U M; Peters, Dorothea M; Weissmann, Norbert; Kaschtanow, Andre; Schermuly, Ralph T; Michurina, Tatyana V; Enikolopov, Grigori; Müller, Dieter; Mietens, Andrea; Middendorff, Ralf

    2016-03-01

    Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor β and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension. PMID:26699726

  12. Expression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension

    PubMed Central

    Gackowska, Lidia; Litwin, Mieczyslaw; Trojanek, Joanna; Eljaszewicz, Andrzej; Kubiszewska, Izabela; Niemirska, Anna; Wierzbicka, Aldona; Michalkiewicz, Jacek

    2015-01-01

    The aim of the study was to find out whether peripheral blood leukocyte adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) protein expression patterns (flow cytometry) differ between the primary hypertension children (n = 57) and healthy controls (n = 19) and if their expression levels are related to selected clinical parameters. The group of 26 patients [AdipoR(−)] showed lower and the group of 31 patients [AdipoR(+)] showed higher AdipoRs protein expression than the control and each other (P < 0.01 for neutrophils, P < 0.05 for monocytes). The AdipoR(+) leukocytes expressed higher AdipoR1 mRNA levels (RT-PCR) than AdipoR(−) ones and controls (P = 0.022 and P = 0.007, resp.). Despite greater BMI, the AdipoR(−) patients had unchanged serum adiponectin levels. In contrast, AdipoR(+) patients had lower serum adiponectin concentrations than the AdipoR(−) ones and controls (P < 0.001). The AdipoR(+) patients had higher blood pressure (P = 0.042) and greater carotid intima-media thickness (P = 0.017) than the AdipoR(−) ones. The stage of hypertension was associated with increased neutrophil but not monocyte AdipoR1 density (AdipoR1 MFI) (P < 0.05). Severe ambulatory hypertension was presented more often in AdipoR(+) patients than in AdipoR(−) ones (51.6% versus 26.9%, resp.; P < 0.01). In conclusion, neutrophil AdipoRs upregulation was associated with early stages of vascular injury, hypertension severity, and low serum levels of adiponectin. PMID:26146630

  13. Effect of Huanglian Jiedu Decoction on Thoracic Aorta Gene Expression in Spontaneous Hypertensive Rats

    PubMed Central

    Yue, Gui-Hua; Zhuo, Shao-Yuan; Zhang, Zhuo; Gao, Yi-Wen; Luo, Yuan

    2014-01-01

    Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats. Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray. Results. Hypertension induced 441 genes upregulated and 417 genes downregulated compared with the normal control group. Treatment of HJD resulted in 76 genes downregulated and 20 genes upregulated. GC data analysis showed that the majority of change genes were involved in immune system process, developmental process, and cell death. Conclusion. Hypertension altered expression of many genes that regulate various biological functions. HJD significantly reduced hypertension and altered the gene expression profiles of SHR rats. These changing genes were involved in many cellular functions such as regulating smooth muscle contraction, Ca(2+) homeostasis, and NO pathway. This study provides the potential novel insights into hypertension and antihypertension effects of HJD. PMID:24744811

  14. Expression of Heat Shock Protein 70 Gene and Its Correlation with Inflammatory Markers in Essential Hypertension

    PubMed Central

    Srivastava, Kamna; Narang, Rajiv; Bhatia, Jagriti; Saluja, Daman

    2016-01-01

    Objectives Hypertension is characterized by systemic high blood pressure and is the most common and important risk factor for the development of cardiovascular diseases. Studies have shown that the circulating levels of certain inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interlukin-6 (IL-6), c-reactive protein (CRP), and tumor suppressor protein-53 (p53) are upregulated and are independently associated with essential hypertension. However, mechanism of increase in the levels of HSP70 protein is not clear. No such studies are reported in the blood circulation of patients with essential hypertension. In the present study, we investigated the expression of circulating HSP70 at mRNA and protein levels and its relationship with other inflammatory markers in patients with essential hypertension. Materials and Methods We recruited 132 patients with essential hypertension and 132 normal controls from similar socio-economic-geographical background. The expression of HSP70 at mRNA levels was determined by Real Time PCR and at protein levels by indirect Elisa and Western Blot techniques. Results We found a significantly higher expression of HSP70 gene expression (approximately 6.45 fold, P < 0.0001) in hypertensive patients as compared to healthy controls. A significant difference (P < 0.0001) in the protein expression of HSP70 was also observed in plasma of patients as compared to that of controls. Conclusion Higher expression of HSP70 is positively correlated with inflammatory markers in patients with essential hypertension and this correlation could play an important role in essential hypertension. PMID:26989902

  15. Calcium homeostasis is altered in skeletal muscle of spontaneously hypertensive rats: cytofluorimetric and gene expression analysis.

    PubMed

    Liantonio, Antonella; Camerino, Giulia M; Scaramuzzi, Antonia; Cannone, Maria; Pierno, Sabata; De Bellis, Michela; Conte, Elena; Fraysse, Bodvael; Tricarico, Domenico; Conte Camerino, Diana

    2014-10-01

    Hypertension is often associated with skeletal muscle pathological conditions related to function and metabolism. The mechanisms underlying the development of these pathological conditions remain undefined. Because calcium homeostasis is a biomarker of muscle function, we assessed whether it is altered in hypertensive muscles. We measured resting intracellular calcium and store-operated calcium entry (SOCE) in fast- and slow-twitch muscle fibers from normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) by cytofluorimetric technique and determined the expression of SOCE gene machinery by real-time PCR. Hypertension caused a phenotype-dependent dysregulation of calcium homeostasis; the resting intracellular calcium of extensor digitorum longus and soleus muscles of SHRs were differently altered with respect to the related muscle of normotensive animals. In addition, soleus muscles of SHR showed reduced activity of the sarcoplasmic reticulum and decreased sarcolemmal calcium permeability at rest and after SOCE activation. Accordingly, we found an alteration of the expression levels of some SOCE components, such as stromal interaction molecule 1, calcium release-activated calcium modulator 1, and transient receptor potential canonical 1. The hypertension-induced alterations of calcium homeostasis in the soleus muscle of SHRs occurred with changes of some functional outcomes as excitability and resting chloride conductance. We provide suitable targets for therapeutic interventions aimed at counterbalancing muscle performance decline in hypertension, and propose the reported calcium-dependent parameters as indexes to predict how the antihypertensive drugs could influence muscle function. PMID:25084345

  16. The Normalisation of Homeschooling in the USA

    ERIC Educational Resources Information Center

    Stevens, Mitchell L.

    2003-01-01

    Home education emerged as a deviant practice in the USA in the late 1970s and became an acceptable alternative to conventional schooling in a remarkably short period of time. This paper argues that the trajectory of normalisation has been shaped by cultural and institutional features peculiar to the US national context. The paper also offers…

  17. Cardiac angiotensin-(1-12) expression and systemic hypertension in rats expressing the human angiotensinogen gene.

    PubMed

    Ferrario, Carlos M; VonCannon, Jessica; Jiao, Yan; Ahmad, Sarfaraz; Bader, Michael; Dell'Italia, Louis J; Groban, Leanne; Varagic, Jasmina

    2016-04-15

    Angiotensin-(1-12) [ANG-(1-12)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG-(1-12) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats (n= 11), male homozygous TGR(hAGT)L1623 (n= 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1-12) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1-12) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function. PMID:26873967

  18. Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Hassanpour, Hossein; Khalaji-Pirbalouty, Valiallah; Nasiri, Leila; Mohebbi, Abdonnaser; Bahadoran, Shahab

    2015-11-01

    To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control ( P < 0.05). In the hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) ( P < 0.05). Glutathione peroxidase activity did not change. Relative gene expression of catalase and superoxide dismutases (1 and 2) was downregulated, while glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension.

  19. Comprehensive Gene Expression Profiling Reveals Synergistic Functional Networks in Cerebral Vessels after Hypertension or Hypercholesterolemia

    PubMed Central

    Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon

    2013-01-01

    Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591

  20. Immune cell CD62L and CD11a expression in response to a psychological stressor in human hypertension.

    PubMed

    Mills, Paul J; Farag, Noha H; Hong, Suzi; Kennedy, Brian P; Berry, Charles C; Ziegler, Michael G

    2003-08-01

    This study examined the effects of hypertension and an acute psychological stressor on white blood cells and their expression of CD62L and CD11a. Seventeen mild hypertensive and 23 normotensive volunteers were studied prior to and following a standardized laboratory public speech. In response to the speech, all subjects increased the number of circulating leukocyte populations (p's<.01). Patients with hypertension increased the number of circulating white blood cells more than normotensives (p<.01). Hypertensives also showed a greater increase in the number of circulating CD3(+)CD8(+) T cells (p<.02) in response to the speech. Only hypertensives increased the number of circulating CD8(+)CD62L(high) T cells (p=.001). The density of CD11a on lymphocytes was increased in all subjects following the speech (p<.001). Hypertensives showed a greater mean density of CD11a on lymphocytes (p<.01). Coupled with observations of increased expression of the endothelial CD11a ligand ICAM-1 in hypertension, these findings are consistent with the notion that patients with hypertension exhibit a circulatory environment conducive to increased leukocyte adhesion. Exposure to repeated psychological stressors may further augment this potentially adverse circulatory environment. PMID:12831828

  1. Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

    PubMed Central

    VASHUKOVA, ELENA S.; GLOTOV, ANDREY S.; FEDOTOV, PAVEL V.; EFIMOVA, OLGA A.; PAKIN, VLADIMIR S.; MOZGOVAYA, ELENA V.; PENDINA, ANNA A.; TIKHONOV, ANDREI V.; KOLTSOVA, ALLA S.; BARANOV, VLADISLAV S.

    2016-01-01

    Pre-eclampsia (PE) is a complication of pregnancy that affects 5–8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP-miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR-518a, miR-527, miR-518e and miR-4532) and 2 downregulated (miR-98 and miR-135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis. PMID:27176897

  2. Placental microRNA expression in pregnancies complicated by superimposed pre‑eclampsia on chronic hypertension.

    PubMed

    Vashukova, Elena S; Glotov, Andrey S; Fedotov, Pavel V; Efimova, Olga A; Pakin, Vladimir S; Mozgovaya, Elena V; Pendina, Anna A; Tikhonov, Andrei V; Koltsova, Alla S; Baranov, Vladislav S

    2016-07-01

    Pre-eclampsia (PE) is a complication of pregnancy that affects 5‑8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP‑miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR‑518a, miR‑527, miR‑518e and miR‑4532) and 2 downregulated (miR‑98 and miR‑135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis. PMID:27176897

  3. Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension.

    PubMed

    Nozik-Grayck, Eva; Woods, Crystal; Stearman, Robert S; Venkataraman, Sujatha; Ferguson, Bradley S; Swain, Kalin; Bowler, Russell P; Geraci, Mark W; Ihida-Stansbury, Kaori; Stenmark, Kurt R; McKinsey, Timothy A; Domann, Frederick E

    2016-07-01

    Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2'-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression. PMID:27233998

  4. Protein disulfide isomerase expression increases in resistance arteries during hypertension development. Effects on Nox1 NADPH oxidase signaling

    PubMed Central

    Androwiki, Aline C. D.; Camargo, Lívia de Lucca; Sartoretto, Simone; Couto, Gisele K.; Ribeiro, Izabela M. R.; Veríssimo-Filho, Sidney; Rossoni, Luciana V.; Lopes, Lucia R.

    2015-01-01

    NADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular smooth muscle cells. However, the role of PDI in conductance and resistance arteries during hypertension development remains unknown. The aim of the present study was to investigate PDI expression and NADPH oxidase dependent ROS generation during hypertension development. Mesenteric resistance arteries (MRA) and thoracic aorta were isolated from 6, 8, and 12 week-old spontaneously hypertensive (SHR) and Wistar rats. ROS production (dihydroethidium fluorescence), PDI (WB, imunofluorescence), Nox1 and NOX4 (RT-PCR) expression were evaluated. Results show a progressive increase in ROS generation in MRA and aorta from 8 to 12 week-old SHR. This effect was associated with a concomitant increase in PDI and Nox1 expression only in MRA. Therefore, suggesting a positive correlation between PDI and Nox1 expression during the development of hypertension in MRA. In order to investigate if this effect was due to an increase in arterial blood pressure, pre hypertensive SHR were treated with losartan (20 mg/kg/day for 30 days), an AT1 receptor antagonist. Losartan decreased blood pressure and ROS generation in both vascular beds. However, only in SHR MRA losartan treatment lowered PDI and Nox1 expression to control levels. In MRA PDI inhibition (bacitracin, 0.5 mM) decreased Ang II redox signaling (p-ERK 1/2). Altogether, our results suggest that PDI plays a role in triggering oxidative stress and vascular dysfunction in resistance but not in conductance arteries, increasing Nox1 expression and activity. Therefore, PDI could be a new player in oxidative stress and functional alterations in resistance arteries during the establishment of hypertension. PMID:25870854

  5. Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients

    PubMed Central

    Alvarez-Aguilar, Cleto; Alvarez-Paredes, Alfonso Rafael; Lindholm, Bengt; Stenvinkel, Peter; García-López, Elvia; Mejía-Rodríguez, Oliva; López-Meza, Joel Edmundo; Amato, Dante; Paniagua, Ramon

    2013-01-01

    Background A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. Methods Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). Results A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. Conclusion These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients. PMID:24348062

  6. Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

    PubMed Central

    Tong, Sheng; Neboori, Hanmanth J.; Tran, Edward D.; Schmid-Schönbein, Geert W.

    2011-01-01

    Background/Aims: Leukocyte adhesion to the endothelium is abnormal in hypertension. We have recently shown that spontaneously hypertensive rats (SHRs) have circulating leukocytes with enhanced CD18 receptor cleavage. In the current study, we investigate expression levels of its counter receptor, intercellular adhesion molecule (ICAM-1), and its possible proteolytic cleavage in the SHR and control Wistar rat. Methods ICAM-1 was labeled on tissue sections with two antibodies targeting its extracellular and intracellular domains and evaluated by light absorption measurements. The in situ cleavage of ICAM-1 was assessed by treating vessel sections with matrix metalloproteinase (MMP)-7, MMP-9 and elastase. Results SHRs showed a significant increase in ICAM-1 expression in liver and kidney compared with Wistar rats. The liver and kidney glomeruli exhibit a discrepancy in label density between intra- and extracellular antibodies, which suggests that enzymatic cleavage may be a factor determining ICAM-1 distribution. MMP-7 and MMP-9, which are elevated in SHR plasma, and elastase, which has elevated activity in SHR neutrophils, cleave the extracellular domain of ICAM-1 when applied to the tissue. Conclusion ICAM-1 expression in SHRs is upregulated in a tissue-specific manner. Proteolytic cleavage of the extracellular domain of ICAM-1 and accumulation in kidney glomeruli may play a role in the renal involvement of inflammation. PMID:21464573

  7. A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

    PubMed Central

    Chen, Brian H.; Liu, Chunyu; Joehanes, Roby; Johnson, Andrew D.; Yao, Chen; Ying, Sai-xia; Courchesne, Paul; Milani, Lili; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Reinmaa, Eva; Dehghan, Abbas; Hofman, Albert; Uitterlinden, André G.; Hernandez, Dena G.; Bandinelli, Stefania; Singleton, Andrew; Melzer, David; Metspalu, Andres; Carstensen, Maren; Grallert, Harald; Herder, Christian; Meitinger, Thomas; Peters, Annette; Roden, Michael; Waldenberger, Melanie; Dörr, Marcus; Felix, Stephan B.; Zeller, Tanja; Vasan, Ramachandran; O'Donnell, Christopher J.; Munson, Peter J.; Yang, Xia; Prokisch, Holger; Völker, Uwe; van Meurs, Joyce B. J.; Ferrucci, Luigi; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension. PMID:25785607

  8. A meta-analysis of gene expression signatures of blood pressure and hypertension.

    PubMed

    Huan, Tianxiao; Esko, Tõnu; Peters, Marjolein J; Pilling, Luke C; Schramm, Katharina; Schurmann, Claudia; Chen, Brian H; Liu, Chunyu; Joehanes, Roby; Johnson, Andrew D; Yao, Chen; Ying, Sai-Xia; Courchesne, Paul; Milani, Lili; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Reinmaa, Eva; Dehghan, Abbas; Hofman, Albert; Uitterlinden, André G; Hernandez, Dena G; Bandinelli, Stefania; Singleton, Andrew; Melzer, David; Metspalu, Andres; Carstensen, Maren; Grallert, Harald; Herder, Christian; Meitinger, Thomas; Peters, Annette; Roden, Michael; Waldenberger, Melanie; Dörr, Marcus; Felix, Stephan B; Zeller, Tanja; Vasan, Ramachandran; O'Donnell, Christopher J; Munson, Peter J; Yang, Xia; Prokisch, Holger; Völker, Uwe; van Meurs, Joyce B J; Ferrucci, Luigi; Levy, Daniel

    2015-03-01

    Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension. PMID:25785607

  9. Egr-1 Expression During Neointimal Development in Flow-Associated Pulmonary Hypertension

    PubMed Central

    Dickinson, Michael G.; Bartelds, Beatrijs; Molema, Grietje; Borgdorff, Marinus A.; Boersma, Bibiche; Takens, Janny; Weij, Michel; Wichers, Pieter; Sietsma, Hannie; Berger, Rolf M.F.

    2011-01-01

    In flow-associated pulmonary arterial hypertension (PAH), increased pulmonary blood flow is an essential trigger for neointimal formation. Using microarray analysis, we recently found that the early growth response protein 1 (Egr-1) transcription factor is increased in experimental flow-associated end-stage PAH. Its role in PAH development is unknown. Here, we assessed the spatiotemporal expression of Egr-1 during neointimal development in flow-associated PAH. Flow-associated PAH was produced in rats by combining monocrotaline administration with an aortocaval shunt. Animals were sacrificed 1 day before or 1 day, 1 week, or 4 to 5 weeks after flow addition. Egr-1 expression was spatiotemporally assessed using laser microdissection, quantitative real-time PCR and immunohistochemistry. In addition, Egr-1 expression was assessed in a non-neointimal pulmonary hypertension model and in human PAH associated with congenital shunt. In 4 to 5 weeks, rats subjected to increased flow developed PAH with neointimal lesions. Egr-1 mRNA was increased 1 day after flow addition and in end-stage PAH, whereas monocrotaline only did not result in increased Egr-1 mRNA. Directly after flow addition, Egr-1 was expressed in endothelial cells. During disease development, Egr-1 protein expression increased and migrated throughout the vessel wall. In PAH patients, Egr-1 was expressed in vessels with media hypertrophy and neointimal lesions, including plexiform lesions. Thus, Egr-1 may be an important regulator in the development of pulmonary neointimal lesions induced by increased pulmonary blood flow. PMID:21924231

  10. Egr-1 expression during neointimal development in flow-associated pulmonary hypertension.

    PubMed

    Dickinson, Michael G; Bartelds, Beatrijs; Molema, Grietje; Borgdorff, Marinus A; Boersma, Bibiche; Takens, Janny; Weij, Michel; Wichers, Pieter; Sietsma, Hannie; Berger, Rolf M F

    2011-11-01

    In flow-associated pulmonary arterial hypertension (PAH), increased pulmonary blood flow is an essential trigger for neointimal formation. Using microarray analysis, we recently found that the early growth response protein 1 (Egr-1) transcription factor is increased in experimental flow-associated end-stage PAH. Its role in PAH development is unknown. Here, we assessed the spatiotemporal expression of Egr-1 during neointimal development in flow-associated PAH. Flow-associated PAH was produced in rats by combining monocrotaline administration with an aortocaval shunt. Animals were sacrificed 1 day before or 1 day, 1 week, or 4 to 5 weeks after flow addition. Egr-1 expression was spatiotemporally assessed using laser microdissection, quantitative real-time PCR and immunohistochemistry. In addition, Egr-1 expression was assessed in a non-neointimal pulmonary hypertension model and in human PAH associated with congenital shunt. In 4 to 5 weeks, rats subjected to increased flow developed PAH with neointimal lesions. Egr-1 mRNA was increased 1 day after flow addition and in end-stage PAH, whereas monocrotaline only did not result in increased Egr-1 mRNA. Directly after flow addition, Egr-1 was expressed in endothelial cells. During disease development, Egr-1 protein expression increased and migrated throughout the vessel wall. In PAH patients, Egr-1 was expressed in vessels with media hypertrophy and neointimal lesions, including plexiform lesions. Thus, Egr-1 may be an important regulator in the development of pulmonary neointimal lesions induced by increased pulmonary blood flow. PMID:21924231

  11. Effects of phased joint intervention on Rho/ROCK expression levels in patients with portal hypertension

    PubMed Central

    Shi, Min; Wei, Jue; Meng, Wen-Ying; Wang, Na; Wang, Ting; Wang, Yu-Gang

    2016-01-01

    The current study investigated the effects of phased joint intervention on clinical efficacy and Rho/Rho-associated coil protein kinase (ROCK) expression in patients with portal hypertension complicated by esophageal variceal bleeding (EVB) and hypersplenism. Patients with portal hypertension (n=53) caused by liver cirrhosis complicated by EVB and hypersplenism treated with phased joint intervention were assessed, and portal hemodynamics, blood, liver function, complications, and rebleeding incidence were analyzed. Reverse transcription-quantitative polymerase chain reaction was used to measure Rho, ROCK1 and ROCK2 mRNA expression levels in peripheral blood mononuclear cells prior to and following phased joint intervention, and western blotting was employed to determine the protein expression levels of Rho, ROCK1, ROCK2, phosphorylated (p) myosin phosphatase target subunit 1 (MYPT1) and total-MYPT1. All patients underwent an emergency assessment of hemostasis with a 100% success rate. Varicose veins were alleviated, and portal hemodynamics and liver function improved following intervention. Furthermore, preoperative and postoperative expression levels of Rho, ROCK1 and ROCK2 mRNA were higher compared with the control group. Notably, the mRNA expression levels of Rho, ROCK1 and ROCK2 in the postoperative group were significantly lower when compared with the preoperative group. Protein expression levels of Rho, ROCK1, ROCK2 and pMYPT1 in the postoperative group were lower, as compared with the preoperative group. Concentration levels of transforming growth factor-β1, connective tissue growth factor and platelet-derived growth factor in peripheral blood were significantly reduced following phased joint intervention. Therefore, the present findings demonstrated that phased joint intervention is able to effectively treat EVB and hypersplenism, and improve liver function. The efficacy of phased joint intervention may be associated with its role in the regulation of the

  12. Periostin expression induced by oxidative stress contributes to myocardial fibrosis in a rat model of high salt-induced hypertension

    PubMed Central

    WU, HAN; CHEN, LIANG; XIE, JUN; LI, RAN; LI, GUAN-NAN; CHEN, QIN-HUA; ZHANG, XIN-LIN; KANG, LI-NA; XU, BIAO

    2016-01-01

    Periostin is an extracellular matrix protein involved in fibrosis. The present study investigated the importance of periostin in hypertension-induced myocardial fibrosis. Rats were randomly divided into either the normal group (0.4% NaCl diet; n=8) or hypertension group (8% NaCl diet; n=8). For 36 weeks, the blood pressure and heart rate of the rats were monitored. At week 36, the hearts were extracted for further analysis. Masson's staining and western blotting were performed to determine the levels of periostin protein expression, oxidative stress and fibrosis. In addition, fibroblasts were isolated from adult rats and cultured in vitro, and following treatment with angiotensin II (Ang II) and N-acetyl-L-cysteine (NAC), western blotting, immunofluorescence and 2′,7′ dichlorodihydrofluorescin staining were performed to examine reactive oxygen species production, and periostin and α-smooth muscle actin (α-SMA) expression levels. The results demonstrated that periostin expression and oxidative stress were increased in hypertensive hearts compared with normal hearts. The in vitro experiments demonstrated that Ang II upregulated the expression levels of periostin and α-SMA compared with the control, whereas, pretreatment with NAC inhibited oxidative stress, periostin and α-SMA expression in fibroblasts. In conclusion, the results of the current study suggested that oxidative stress-induced periostin is involved in myocardial fibrosis and hypertension. The present study demonstrated that periostin inhibition may be a promising approach for the inhibition of hypertension-induced cardiac remodeling. PMID:27220372

  13. Gene Expression Suggests Spontaneously Hypertensive Rats May Have Altered Metabolism and Reduced Hypoxic Tolerance

    PubMed Central

    Ritz, Marie-Françoise; Grond-Ginsbach, Caspar; Engelter, Stefan; Lyrer, Philippe

    2012-01-01

    Cerebral small vessel disease (SVD) is an important cause of stroke, cognitive decline and vascular dementia (VaD). It is associated with diffuse white matter abnormalities and small deep cerebral ischemic infarcts. The molecular mechanisms involved in the development and progression of SVD are unclear. As hypertension is a major risk factor for developing SVD, Spontaneously Hypertensive Rats (SHR) are considered an appropriate experimental model for SVD. Prior work suggested an imbalance between the number of blood microvessels and astrocytes at the level of the neurovascular unit in 2-month-old SHR, leading to neuronal hypoxia in the brain of 9-month-old animals. To identify genes and pathways involved in the development of SVD, we compared the gene expression profile in the cortex of 2 and 9-month-old of SHR with age-matched normotensive Wistar Kyoto (WKY) rats using microarray-based technology. The results revealed significant differences in expression of genes involved in energy and lipid metabolisms, mitochondrial functions, oxidative stress and ischemic responses between both groups. These results strongly suggest that SHR suffer from chronic hypoxia, and therefore are unable to tolerate ischemia-like conditions, and are more vulnerable to high-energy needs than WKY. This molecular analysis gives new insights about pathways accounting for the development of SVD. PMID:22272763

  14. The Normalised Child: A Non-Traditional Psychological Framework

    ERIC Educational Resources Information Center

    Grebennikov, Leonid

    2005-01-01

    The terms "normalisation" and "normalised child" were introduced into early childhood scholarship by Maria Montessori, whose ideas regarding norm and deviation in children's development and behaviour have been discussed, debated and sometimes criticised, but remain magnetic and recognised worldwide. Contemporary Western society is witnessing a…

  15. Expression of mutant bone morphogenetic protein receptor II worsens pulmonary hypertension secondary to pulmonary fibrosis

    PubMed Central

    Robinson, Linda J.; Moore, Christy S.; Blackwell, Thomas R.; Gladson, Santhi; Penner, Niki L.; Burman, Ankita; McClellan, Lucas J.; Polosukhin, Vasiliy V.; Tanjore, Harikrishna; McConaha, Melinda E.; Gleaves, Linda A.; Talati, Megha A.; Hemnes, Anna R.; Fessel, Joshua P.; Lawson, William E.; Blackwell, Timothy S.; West, James D.

    2015-01-01

    Abstract Pulmonary fibrosis is often complicated by pulmonary hypertension (PH), and previous studies have shown a potential link between bone morphogenetic protein receptor II (BMPR2) and PH secondary to pulmonary fibrosis. We exposed transgenic mice expressing mutant BMPR2 and control mice to repetitive intraperitoneal injections of bleomycin for 4 weeks. The duration of transgene activation was too short for mutant BMPR2 mice to develop spontaneous PH. Mutant BMPR2 mice had increased right ventricular systolic pressure compared to control mice, without differences in pulmonary fibrosis. We found increased hypoxia-inducible factor (HIF)1-α stabilization in lungs of mutant-BMPR2-expressing mice compared to controls following bleomycin treatment. In addition, expression of the hypoxia response element protein connective tissue growth factor was increased in transgenic mice as well as in a human pulmonary microvascular endothelial cell line expressing mutant BMPR2. In mouse pulmonary vascular endothelial cells, mutant BMPR2 expression resulted in increased HIF1-α and reactive oxygen species production following exposure to hypoxia, both of which were attenuated with the antioxidant TEMPOL. These data suggest that expression of mutant BMPR2 worsens secondary PH through increased HIF activity in vascular endothelium. This pathway could be therapeutically targeted in patients with PH secondary to pulmonary fibrosis. PMID:26697175

  16. Correlative studies on the effects of obesity, diabetes and hypertension on gene expression in omental adipose tissue of obese women

    PubMed Central

    Fain, J N

    2011-01-01

    Objective: A major consequence of obesity is the enormous expansion of and enhanced inflammatory response seen in visceral adipose tissue. I hypothesized that the expression of inflammatory markers in visceral omental fat would correlate with the extent of visceral adiposity as measured by waist circumference or body mass index and that diabetes and hypertension, defined as subjects taking anti-hypertensive drugs, would be associated with changes in mRNA expression in visceral fat. Design and methods: The expression of 106 mRNAs by RT-PCR was examined in observational studies using extracts of omental fat of obese women undergoing bariatric surgery as well as the circulating levels of some adipokines. We also compared the mRNA levels of 65 proteins in omental fat removed during gastric bypass surgery of women with and without hypertension and those with type 2 diabetes. Results: Out of 106 mRNAs the expression of 10 mRNAs in omental fat of women not taking anti-hypertensive drugs correlated with waist circumference while 7 different mRNAs had significant correlations with circulating glucose. The correlations of waist circumference with mRNA expression were abolished, except for interleukin (IL)-1 receptor antagonist (IL-1RA), in women taking anti-hypertensive drugs. The correlations of blood glucose with omental fat mRNA expression were abolished, except for that of Akt1 and Akt2, in women taking anti-hypertensive drugs. However, the expression of 4 different mRNAs in omental fat was affected by circulating glucose in subjects taking anti-hypertensive drugs. The circulating levels of IL-1 RA, but not fatty acid binding protein 4, adipsin and phospholipase A2, correlated with both waist circumference and mRNA expression in omental fat. Conclusion: In female bariatric surgery patients, the mRNA expression of some proteins in omental fat was affected by the degree of obesity, whereas hypertension and diabetes affected a separate set of mRNAs. PMID:23154658

  17. Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity.

    PubMed

    Subramanian, Meenakumari; Hunt, Adam L; Petrucci, Giuseppe A; Chen, Zengyi; Hendley, Edith D; Palmer, Bradley M

    2014-07-01

    The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca(2+), Cu(2+), Mg(2+) and Zn(2+), which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats. PMID:24629670

  18. Decreased expression of transient receptor potential channels in cerebral vascular tissue from patients after hypertensive intracerebral hemorrhage.

    PubMed

    Thilo, Florian; Suess, Olaf; Liu, Ying; Tepel, Martin

    2011-01-01

    Recent data indicate that transient receptor potential (TRP) cation channels play an important role in hypertension. Now, we tested the hypothesis that TRP expression is altered in human cerebral vascular tissue in patients who had experienced hypertensive intracerebral hemorrhage. TRPC1, TRPC3, TRPC5, TRPC6, TRPM4, TRPM6, and TRPM7 channels were detected in cerebral vascular tissue by quantitative real-time RT-PCR. Control cerebral vascular tissue was obtained from normotensive patients who underwent neurosurgical operation because of brain tumor. To examine a possible relation between the expression of TRP expression and hypoxic conditions caused by the intracerebral bleeding, we examined the expression of hypoxia inducible factor 1a (HIF1a). Transcripts of TRPC3, TRPC5, TRPM6, and HIF1a were significantly reduced in cerebral vascular tissue from patients after hypertensive intracerebral hemorrhage compared to controls. TRPC3 mRNA correlated well with the expression of HIF1a mRNA (r(2) = 0.59; p = 0.01). TRPC3 expression is associated with hypertension and hypoxic conditions in human cerebral vascular tissue. PMID:21957871

  19. Abnormal expression of vesicular transport proteins in pulmonary arterial hypertension in monocrotaline-treated rats.

    PubMed

    Zhang, Hongliang; Luo, Qin; Liu, Zhihong; Wang, Yong; Zhao, Zhihui

    2015-03-01

    Intracellular vesicular transport is shown to be dysfunctional in pulmonary arterial hypertension (PAH). However, the expression of intracellular vesicular transport proteins in PAH remains unclear. To elucidate the possible role of these proteins in the development of PAH, the changes in the expressions of N-ethyl-maleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP), synaptosome-associated membrane protein 23 (SNAP23), type 2 bone morphogenetic receptor (BMPR2), caveolin-1 (cav-1), and endothelial nitric oxide synthase (eNOS) were examined in lung tissues of monocrotaline (MCT)-treated rats by real-time polymerase chain reaction and western blot analysis. In addition, caspase-3, also examined by western blot analysis, was used as an indicator of apoptosis. Our data showed that during the development of PAH, the expressions of NSF, α-SNAP, and SNAP23 were significantly increased before pulmonary arterial pressure started to increase and then significantly decreased after PAH was established. The expressions of BMPR2 and eNOS were similar to those of NSF, α-SNAP, and SNAP23; however, the expression of cav-1 was down-regulated after MCT treatment. Caspase-3 expression was increased after exposure to MCT. In conclusion, the expressions of NSF, α-SNAP, and SNPA23 changed greatly during the onset of PAH, which was accompanied by abnormal expressions of BMPR2, cav-1, and eNOS, as well as an increase in apoptosis. Thus, changes in NSF, α-SNAP, and SNAP23 expressions appear to be mechanistically associated with the development of PAH in MCT-treated rats. PMID:25630652

  20. COMPARATIVE MICROARRAY EXPRESSION ANALYSIS OF SELECTED CANCER RELEVANT GENES IN HYPERTENSIVE RESISTANT VERSUS SUSCEPTIBLE RODENT STRAINS

    EPA Science Inventory

    Hypertension and cancer are prevalent diseases. Epidemiological studies suggest that hypertension may increase the long term risk of cancer. Identification of resistance and/or susceptibility genes using rodent models could provide important insights into the management and treat...

  1. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  2. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

    PubMed Central

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M.; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-01-01

    ABSTRACT The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  3. Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension

    PubMed Central

    Wang, Gang; Yang, Ence; Smith, Kerri J.; Zeng, Yong; Ji, Guoli; Connon, Richard; Fangue, Nann A.; Cai, James J.

    2014-01-01

    Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10−7, hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene—MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research. PMID:25309574

  4. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.

    PubMed

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-04-01

    The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminaryin vitroandin vivoimaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  5. Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension.

    PubMed

    Wang, Gang; Yang, Ence; Smith, Kerri J; Zeng, Yong; Ji, Guoli; Connon, Richard; Fangue, Nann A; Cai, James J

    2014-01-01

    Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10(-7), hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene-MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research. PMID:25309574

  6. Expression and localization of calmodulin-related proteins in brain, heart and kidney from spontaneously hypertensive rats.

    PubMed

    Kameshima, Satoshi; Okada, Muneyoshi; Yamawaki, Hideyuki

    2016-01-15

    Blood pressure is regulated not only by peripheral arterial resistance, but also by heart, kidney, and central nervous system. We have previously demonstrated that expression level of calmodulin-related proteins including eukaryotic elongation factor 2 kinase (eEF2K), death-associated protein kinase (DAPK)3, and histone deacetylase (HDAC)4 was specifically elevated in mesenteric artery from spontaneously hypertensive rats (SHR), which partly contributes to the development of hypertension via vascular inflammation and structural remodeling. We tested the hypothesis whether expression and localization of eEF2K, DAPK3, and HDAC4 are altered in brain, heart, and kidney from SHR. After brain, left ventricles (LV), and kidney were isolated from 12-week-old male Wistar Kyoto rats (WKY) and SHR, Western blotting and histological analysis were performed. In brain tissue, protein expression of eEF2K and HDAC4 was abundant, whereas DAPK3 protein was less. HDAC4 protein expression in SHR brain was significantly higher than that in WKY brain. In LV, protein expression of eEF2K was relatively higher than DAPK3 or HDAC4, and it was significantly higher in SHR than WKY. In kidney tissue, protein expression of DAPK3 was the highest and seemed to be localized specifically to renal tubule. The present results indicate that the increased HDAC4 in brain and increased eEF2K in LV might be at least in part related to the development of hypertension. PMID:26697749

  7. Image quality-based adaptive illumination normalisation for face recognition

    NASA Astrophysics Data System (ADS)

    Sellahewa, Harin; Jassim, Sabah A.

    2009-05-01

    Automatic face recognition is a challenging task due to intra-class variations. Changes in lighting conditions during enrolment and identification stages contribute significantly to these intra-class variations. A common approach to address the effects such of varying conditions is to pre-process the biometric samples in order normalise intra-class variations. Histogram equalisation is a widely used illumination normalisation technique in face recognition. However, a recent study has shown that applying histogram equalisation on well-lit face images could lead to a decrease in recognition accuracy. This paper presents a dynamic approach to illumination normalisation, based on face image quality. The quality of a given face image is measured in terms of its luminance distortion by comparing this image against a known reference face image. Histogram equalisation is applied to a probe image if its luminance distortion is higher than a predefined threshold. We tested the proposed adaptive illumination normalisation method on the widely used Extended Yale Face Database B. Identification results demonstrate that our adaptive normalisation produces better identification accuracy compared to the conventional approach where every image is normalised, irrespective of the lighting condition they were acquired.

  8. Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.

    PubMed

    Leung, Justin Wai-Chung; Wong, Wing Tak; Koon, Hon Wai; Mo, Fong Ming; Tam, Sidney; Huang, Yu; Vanhoutte, Paul M; Chung, Stephen Sum Man; Chung, Sookja Kim

    2011-01-01

    Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ET(A) receptor (BQ123) but not by ET(B) receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ET(A) receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation. PMID:22096514

  9. Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks.

    PubMed

    Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

    2012-11-01

    Blacks represent a high-risk population for salt-sensitive hypertension and heart disease, but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in blacks with hypertension and cardiac hypertrophy. In this study, we tested the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type (WT) or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout (KO) background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of proatrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12 to 14 months of age when fed a normal salt diet or at a younger age when fed a high-salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in blacks who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in blacks. PMID:22987923

  10. UPREGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN NODOSE GANGLIA AND THE LOWER BRAINSTEM OF HYPERTENSIVE RATS

    PubMed Central

    Vermehren-Schmaedick, Anke; Jenkins, Victoria K.; Hsieh, Hui-ya; Brown, Alexandra L.; Page, Mollie P.; Brooks, Virginia L.; Balkowiec, Agnieszka

    2014-01-01

    Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension: the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared to age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension. PMID:23172808

  11. Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats.

    PubMed

    Vermehren-Schmaedick, Anke; Jenkins, Victoria K; Hsieh, Hui-ya; Brown, Alexandra L; Page, Mollie P; Brooks, Virginia L; Balkowiec, Agnieszka

    2013-02-01

    Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension, the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared with age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension. PMID:23172808

  12. Ocular Hypertension

    MedlinePlus

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Written by: Kierstan Boyd Reviewed by: J Kevin ...

  13. [Effect of carvedilol in the combination with quercetine and tiotriazoline on the nucleus density and RNA concentration in the nucleus of cardiac myocytes of spontaneous hypertensive rats].

    PubMed

    Zahorodnyĭ, M I

    2010-01-01

    It was found out in the previous studies, that rats with spontaneous hypertension (SHR) developed the hypertrophy of myocardium, disorders of osmotic properties of erythrocytes membranes, morphological and ultrastructural changes in the cardiac hystiocytes of animals. Carvedilol in SHR rats has decreased blood pressure, and normalized physiological, biochemical and morphological indexes in the cardiac muscle. More expressed effect was observed during the use of carvedilol with metabolic medications--Quercetine and Tiotriazoline. Studies on SHR rats has shown increase of cardiac hystiocyte nuclei density and decrease in RNA concentration in a cardiac muscle. Carvedilol, Quercetine and Tiotriazoline have normalising effect on investigated parameters. The use of carvedilol with Tiotriazoline have more expressed normalising effect on nuclei density of cardiac hystiocytes, and also on RNA concentration PHK in nuclei of cardiac muscle. PMID:21265126

  14. Can masticatory electromyography be normalised to submaximal bite force?

    PubMed

    Crawford, S R; Burden, A M; Yates, J M; Zioupos, P; Winwood, K

    2015-05-01

    The combination of bite force and jaw muscle electromyography (EMG) provides an insight into the performance of the stomatognathic system, especially in relation to dynamic movement tasks. Literature has extensively investigated possible methods for normalising EMG data encapsulating many different approaches. However, bite force literature trends towards normalising EMG to a maximal voluntary contraction (MVC), which could be difficult for ageing populations or those with poor dental health or limiting conditions such as temporomandibular disorder. The objectives of this study were to (i) determine whether jaw-closing muscle activity is linearly correlated with incremental submaximal and maximal bite force levels and (ii) assess whether normalising maximal and submaximal muscle activity to that produced when performing a low submaximal bite force (20 N) improves repeatability of EMG values. Thirty healthy adults (15 men, 15 women; mean age 21 ± 1·2 years) had bite force measurements obtained using a custom-made button strain gauge load cell. Masseter and anterior temporalis muscle activities were collected bilaterally using surface EMG sensors whilst participants performed maximal biting and three levels of submaximal biting. Furthermore, a small group (n = 4 females) were retested for reliability purposes. Coefficients of variation and intra-class correlation coefficients showed markedly improved reliability when EMG data were normalised compared to non-normalised. This study shows that jaw muscle EMG may be successfully normalised to a very low bite force. This may open possibilities for comparisons between at-risk sample groups that may otherwise find it difficult to produce maximal bite force values. PMID:25600826

  15. Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease.

    PubMed

    Braitsch, Caitlin M; Kanisicak, Onur; van Berlo, Jop H; Molkentin, Jeffery D; Yutzey, Katherine E

    2013-12-01

    During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis were examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is detected with epicardial, perivascular, and interstitial fibrosis, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury. PMID:24140724

  16. Low expression of Gria1 and Grin1 glutamate receptors in the nucleus accumbens of Spontaneously Hypertensive Rats (SHR).

    PubMed

    Diana, Mariana C; Santoro, Marcos L; Xavier, Gabriela; Santos, Camila Mauricio; Spindola, Leticia N; Moretti, Patrícia N; Ota, Vanessa K; Bressan, Rodrigo A; Abilio, Vanessa C; Belangero, Sintia I

    2015-10-30

    The Spontaneously Hypertensive Rat (SHR) strain is a classical animal model for the study of essential hypertension. Recently, our group suggested that this strain could be a useful animal model for schizophrenia, which is a severe mental illness with involvement of glutamatergic system. The aim of this study is to investigate glutamatergic receptors (Gria1 and Grin1) and glycine transporter (Glyt1) gene expression in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of SHR animals. The effects in gene expression of a chronic treatment with antipsychotic drugs (risperidone, haloperidol and clozapine) were also analyzed. Animals were treated daily for 30 days, and euthanized for brain tissue collection. The expression pattern was evaluated by Real Time Reverse-Transcriptase (RT) PCR technique. In comparison to control rats, SHR animals present a lower expression of both NMDA (Grin1) and AMPA (Gria1) gene receptors in the NAcc. Antipsychotic treatments were not able to change gene expressions in any of the regions evaluated. These findings provide evidence for the role of glutamatergic changes in schizophrenia-like phenotype of the SHR strain. PMID:26296755

  17. Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension

    SciTech Connect

    Yu Lunyin; Quinn, Deborah A.; Garg, Hari G.; Hales, Charles A. . E-mail: chales@partners.org

    2006-07-14

    The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDKIs, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57, p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension.

  18. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    EPA Science Inventory

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  19. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  20. Connection between dynamically derived IMF normalisation and stellar populations

    NASA Astrophysics Data System (ADS)

    McDermid, Richard M.

    2015-04-01

    In this contributed talk I present recent results on the connection between stellar population properties and the normalisation of the stellar initial mass function (IMF) measured using stellar dynamics, based on a large sample of 260 early-type galaxies observed as part of the ATLAS3D project. This measure of the IMF normalisation is found to vary non-uniformly with age- and metallicity-sensitive absorption line strengths. Applying single stellar population models, there are weak but measurable trends of the IMF with age and abundance ratio. Accounting for the dependence of stellar population parameters on velocity dispersion effectively removes these trends, but subsequently introduces a trend with metallicity, such that `heavy' IMFs favour lower metallicities. The correlations are weaker than those found from previous studies directly detecting low-mass stars, suggesting some degree of tension between the different approaches of measuring the IMF. Resolving these discrepancies will be the focus of future work.

  1. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension.

    PubMed

    Baserga, Mariana; Hale, Merica A; Wang, Zheng Ming; Yu, Xing; Callaway, Christopher W; McKnight, Robert A; Lane, Robert H

    2007-05-01

    Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11beta-HSD2, and GR mRNA and protein levels, but upregulated expression of MR at birth. At day 21 of life, 11beta-HSD2, GR, and also MR mRNA and protein levels were downregulated. UPI did not affect blood pressures (BP) at day 21 of life but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension. PMID:17272666

  2. Expression of Heme Oxygenase-1 in Thick Ascending Loop of Henle Attenuates Angiotensin II-Dependent Hypertension

    PubMed Central

    Drummond, Heather A.; Gousette, Monette U.; Storm, Megan V.; Abraham, Nader G.; Csongradi, Eva

    2012-01-01

    Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139±3 versus 153±2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments,. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption. PMID:22323644

  3. In vivo left ventricular function and collagen expression in aldosterone/salt-induced hypertension.

    PubMed

    Ramirez-Gil, J F; Delcayre, C; Robert, V; Wassef, M; Trouve, P; Mougenot, N; Charlemagne, D; Lechat, P

    1998-12-01

    Cardiac fibrosis is linked to aldosterone-induced hypertension, but the effects on in vivo left ventricular (LV) function are not established. We studied the relations between in vivo LV function and aldosterone/salt cardiac fibrosis. Adult guinea pigs (GPs) were treated for 3 months with an aldosterone infusion and high-salt diet. This treatment induced arterial hypertension (+35%) and moderate LV hypertrophy (LVH; +60%) without right ventricular (RV) hypertrophy. Echo-Doppler LV assessment demonstrated unaltered cardiac output, stroke volume, or LV relaxation. Type I collagen messenger RNA (mRNA) was significantly increased in both ventricles (LV, +48%; RV, +77%) and accompanied by a significant increase in total collagen deposition (LV, from 0.52% in controls to 4.4% in treated GPs; RV, from 0.82 to 5.5% in treated GPs). Plasma norepinephrine levels increased 2.6-fold (p < 0.01) and correlated with the increase in collagen deposition in both ventricles. Collagen content was not correlated with hypertension or LVH. We conclude that aldosterone administration induces cardiac collagen accumulation and a sympathetic stimulation, which might preserve systolic and diastolic function. PMID:9869498

  4. Differential expression of vasoactive mediators in microparticle-challenged lungs of chickens that differ in susceptibility to pulmonary arterial hypertension.

    PubMed

    Hamal, Krishna R; Wideman, Robert F; Anthony, Nicholas B; Erf, Gisela F

    2010-01-01

    Pulmonary hypertension syndrome (PHS; ascites) in fast growing meat-type chickens (broilers) is characterized by the onset of idiopathic pulmonary arterial hypertension (IPAH) leading to right-sided congestive heart failure and terminal ascites. Intravenous microparticle (MP) injection is a tool used by poultry geneticists to screen for the broilers that are resistant (RES) or susceptible (SUS) to IPAH in a breeding population. MPs occlude pulmonary arterioles and initiate focal inflammation, causing local tissues and responding leukocytes to release vasoactive mediators such as serotonin (5-HT), endothelin-1 (ET-1), and nitric oxide (NO). RT-PCR was used to examine the differences between RES and SUS broilers in terms of gene expression of ET-1, ET receptor types A and B (ET(A) and ET(B)), the serotonin transporter (SERT), serotonin receptors (5-HT(1A), 5-HT(2A), 5-HT(1B), 5-HT(2B)), endothelial NO synthase (eNOS), and inducible NOS (iNOS) in the lungs of these broilers before (0 h) and after (2, 6, 12, 24, and 48 h) MP injection. In SUS broilers MP injection elicited higher (P < 0.05) pulmonary expression of 5-HT(1A), 5-HT(2B), and ET-1, which promote vasoconstriction and proliferation of pulmonary arterial smooth muscle cells (PASMC). In RES broilers the MP injection elicited higher expression of eNOS, iNOS, and ET(B), which promote vasodilation and inhibit PASMC proliferation. These observations support the hypothesis that the resistance of broiler chickens to IPAH may be due to the higher expression of vasoactive mediators that favor enhanced vasodilation and attenuated vasoconstriction during MP injection challenges to the pulmonary vasculature. PMID:19907003

  5. Abnormal expression of NSF, α-SNAP and SNAP23 in pulmonary arterial hypertension in rats treated with monocrotaline

    PubMed Central

    Zhang, Hong-Liang; Liu, Zhi-Hong; Luo, Qin; Wang, Yong; Zhao, Zhi-Hui

    2015-01-01

    Background: Recent researches have shown that dysfunctional intracellular vesicular trafficking exists in pulmonary arterial hypertension (PAH). However, the expression of proteins involved in intracellular vesicular trafficking in pulmonary vasculature in PAH remains unclear. Objective: To elucidate possible roles of proteins involved in intracellular vesicular trafficking in the development of PAH in rats treated with monocrotaline, changes in the expression of N-ethyl-maleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP) and synaptosome-associated membrane protein (SNAP) 23 were examined together with expression of caveolin-1 (cav-1), endogenous nitric oxide synthase (eNOS), type 2 bone morphogenetic receptor (BMPR2) and cellular apoptosis. Methods: The mRNA expression was investigated by real time-PCR and protein expression by immunoblot method in rat lung. Caspase-3 was used as an indicator of cellular apoptosis and examined by immunoblot method. Results: During the development of PAH, mRNA and protein expression of NSF, α-SNAP and SNAP23 all significantly increased before pulmonary arterial pressure started to increase, then all significantly decreased when PAH established. The expression of eNOS and BMPR2 changed similarly, while the mRNA and protein of cav-1 both downregulated after monocrotaline treatment. Caspase-3 was also increased after exposure to monocrotaline. Conclusions: Since the expression of NSF, α-SNAP and SNAP23 changed greatly during the onset of PAH and accompanied with abnormal expression of eNOS, BMPR2 and cav-1 and with enhanced cellular apoptosis, NSF, α-SNAP and SNAP23 appear to be associated with the development of PAH in rats treated with monocrotaline. PMID:25932111

  6. Correlation of gene expression with physiological functions: Examples of pulmonary blood vessel rheology, hypoxic hypertension, and tissue remodeling.

    PubMed

    Huang, W; Sher, Y P; Peck, K; Fung, Y C

    2001-01-01

    Microarray gene chip technology is a powerful invention looking for applications. A general principle is proposed here to direct the power of the technology toward physiology, medicine, and pharmacology. Our principle is to match quantitative measures of gene expression with the trend of mathematical parameters that describe biological functions. Mathematical parameterization is the heart. The procedure is illustrated by lung physiology, including the hypoxic hypertension, rheological properties of the tissues, and the remodeling of the pulmonary arterial wall under hypertensive stress. We show first how to reduce the experimental results on these physiological functions into mathematical formulas, and how the parameters of these formulas describe the functional trends precisely. Then under the assumption that the microarray reveals gene activities quantitatively, we match the trends of the gene activity with the trends of the functional parameters. Genes whose trends do match are interpreted as relevant to the functions. Those that do not match are considered irrelevant to the functions. The more functions we consider, the fewer will be the number of genes that are relevant to all functions. Thus we learn about the generality and specificity of the influence of genes on physiology. PMID:11381166

  7. [The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip Goldblatt hypertension rat].

    PubMed

    Wang, Jing; Chen, Zhi-Jiang; Luo, Can-Qiao; Pan, Jing-Yun

    2002-04-25

    Experiments were performed in male Sprague-Dawley rats (150-200 g). A silver clip (0.2 mm internal diameter) was placed on the left renal artery of rats. After operation the rats were divided into 4 groups sham group, 2K1C (two-kidney one clip) group, 2K1C+Arg (2K1C and L-Arg 150 mg/kg x d(-1) by drinking) group, and 2K1C+NAME (2K1C and L-NAME 10 mg/kg x d(-1) i.p.) group. The animals were studied at two time points (4 and 7 weeks after operation) corresponding to phases I and II of Goldblatt hypertension. The animals were deeply anesthetized with pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was removed, then placed in 25% sucrose in PB for 12 h in a 4 degrees C fridge. The 40 microm coronal slices of brainstems were cut with cryostat, collected in PBS for nNOS study by immunohistochemistry. The results showed that (1) only a few neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal medulla, including the depressor area of the ventral surface of medulla oblongata (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number of nNOS positive neurons in caudal medulla was significantly increased in 2K1C Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive neurons in VSMd and CPA were 2K1C+Arg > 2K1C >2K1C +NAME > sham. (3) L-Arg enhanced the expression of nNOS whereas L-NAME inhibited the expression of nNOS in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt hypertension rats at 4 weeks with that of the rats at 7 weeks. PMID:11973601

  8. Mesenchymal stem cells suppress CaN/NFAT expression in the pulmonary arteries of rats with pulmonary hypertension

    PubMed Central

    LIU, JUNFENG; HAN, ZHIBO; HAN, ZHONGCHAO; HE, ZHIXU

    2015-01-01

    Inflammation and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered the primary pathological feature of pulmonary hypertension (PH). The present study determined that mesenchymal stem cells (MSCs) suppress the expression of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT) in the pulmonary arteries of rats, and this may exert a therapeutic effect on PH. The potential therapeutic effects of MSCs on PH were assessed via the transplantation of human umbilical cord-derived MSCs, which were cultured in serum-free medium, into a monocrotaline (MCT)-induced PH rat model. Subsequently, the expression levels of tumor necrosis factor (TNF)-α in lung tissue and plasma, and of CaN and NFATc2 in pulmonary arteries were assessed. In the rat model of MCT-induced PH, investigated in the present study, TNF-α expression levels were detected in the lung tissue, and the levels of TNF-α in the plasma were increased. Furthermore, in addition to hemodynamic changes and the evident medial hypertrophy of the pulmonary muscular arterioles, CaN and NFATc2 expression levels were significantly upregulated in the pulmonary arteries. In the present study, the transplantation of MSCs, cultured in serum-free medium, decreased the levels of TNF-α in the lung tissue and plasma of rats, and downregulated CaN and NFATc2 expression in the pulmonary arteries. Furthermore, hemodynamic abnormalities and medial hypertrophy of the pulmonary muscular arterioles were notably improved. Therefore, the results of the present study may suggest that the administration of MSCs in PH may suppress the production of TNF-α, and downregulate the expression of CaN and NFATc2 in pulmonary arteries, which may provide an effective treatment for PH by suppressing the pathological proliferation of PASMCs. PMID:26640533

  9. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    PubMed

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. PMID:26585490

  10. [Secondary hypertension].

    PubMed

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice. PMID:26619670

  11. Portal Hypertension

    MedlinePlus

    ... Chronic Hepatitis C Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD NOTE: This is ... Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  12. A normalisation framework for (hyper-)spectral imagery

    NASA Astrophysics Data System (ADS)

    Grumpe, Arne; Zirin, Vladimir; Wöhler, Christian

    2015-06-01

    It is well known that the topography has an influence on the observed reflectance spectra. This influence is not compensated by spectral ratios, i.e. the effect is wavelength dependent. In this work, we present a complete normalisation framework. The surface temperature is estimated based on the measured surface reflectance. To normalise the spectral reflectance with respect to a standard illumination geometry, spatially varying reflectance parameters are estimated based on a non-linear reflectance model. The reflectance parameter estimation has one free parameter, i.e. a low-pass function, which sets the scale of the spatial-variance, i.e. the lateral resolution of the reflectance parameter maps. Since the local surface topography has a major influence on the measured reflectance, often neglected shading information is extracted from the spectral imagery and an existing topography model is refined to image resolution. All methods are demonstrated on the Moon Mineralogy Mapper dataset. Additionally, two empirical methods are introduced that deal with observed systematic reflectance changes in co-registered images acquired at different phase angles. These effects, however, may also be caused by the sensor temperature, due to its correlation with the phase angle. Surface temperatures above 300 K are detected and are very similar to a reference method. The proposed method, however, seems more robust in case of absorptions visible in the reflectance spectrum near 2000 nm. By introducing a low-pass into the computation of the reflectance parameters, the reflectance behaviour of the surfaces may be derived at different scales. This allows for an iterative refinement of the local surface topography using shape from shading and the computation reflectance parameters. The inferred parameters are derived from all available co-registered images and do not show significant influence of the local surface topography. The results of the empirical correction show that both

  13. Dietary approaches to stop hypertension influence on insulin receptor substrate-1gene expression: A randomized controlled clinical trial

    PubMed Central

    Kafeshani, Marzieh; Janghorbani, Mohsen; Salehi, Rasol; Kazemi, Mohammad; Entezari, Mohammad Hasan

    2015-01-01

    Background: Insulin receptor substrate (IRS) Type 1 is a main substrate for the insulin receptor, controls insulin signaling in skeletal muscle, adipose tissue, and the vascular, so it is an important candidate gene for insulin resistance (IR). We aimed to compare the effects of the Dietary Approaches to Stop Hypertension (DASH) and Usual Dietary Advices (UDA) on IRS1 gene expression in women at risk for cardiovascular disease. Materials and Methods: A randomized controlled clinical trial was performed in 44 women at risk for cardiovascular disease. Participants were randomly assigned to a UDA diet or the DASH diet. The DASH diet was rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, and sweets, with a total of 2400 mg/day sodium. The UDA diet was a regular diet with healthy dietary advice. Gene expression was assessed by the real-time polymerase chain reaction at the first of study and after 12 weeks. Independent sample t-test and paired-samples t-test were used to compare means of all variables within and between two groups respectively. Results: IRS1 gene expression was increased in DASH group compared with UDA diet (P = 0.00). Weight and waist circumference decreased in DASH group significantly compared to the UDA group (P < 0.05) but the results between the two groups showed no significant difference. Conclusion: DASH diet increased IRS1 gene expression and probably has beneficial effects on IR risks. PMID:26759568

  14. Increased SUMO-1 expression in response to hypoxia: Interaction with HIF-1α in hypoxic pulmonary hypertension.

    PubMed

    Jiang, Yongliang; Wang, Jing; Tian, Hua; Li, Guang; Zhu, Hao; Liu, Lei; Hu, Ruicheng; Dai, Aiguo

    2015-07-01

    Pulmonary hypertension (PH) develops in 30-70% of chronic obstructive pulmonary disease patients and increases morbidity and mortality. The present study aimed to investigate the regulation of small ubiquitin‑related modifier‑1 (SUMO‑1) expression in response to hypoxia. The experiments were carried out in vitro in rat pulmonary arterial smooth muscle cells (PASMCs) and in vivo using a rat hypoxic PH (HPH) model. A significant increase in SUMO‑1 mRNA and protein levels was observed following hypoxic stimulation in vivo and in vitro. SUMO‑1 is known to interact with various transcription factors, including hypoxia‑inducible factor‑1α (HIF‑1α) in vitro. Notably, the expression of HIF‑1α and its target gene, vascular endothelial growth factor, was increased by hypoxia in HPH. In addition, the present data suggest that SUMO‑1 regulated HIF‑1α in response to hypoxia (gene silencing and overexpression). Finally, the co‑immunoprecipitation assays suggest a direct and specific interaction between SUMO‑1 and HIF‑1α. In conclusion, SUMO‑1 may participate in the modulation of HIF‑1α through sumoylation in HPH. However, further studies are required to confirm this. PMID:25976847

  15. Role of PKCδ in Enhanced Expression of Gqα/PLCβ1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats

    PubMed Central

    Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B.

    2016-01-01

    Gqα signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqα and PKCδ activation. We recently showed the role of enhanced expression of Gqα/PLCβ1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCδ in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCδ and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCδ-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCδ. In addition, knocking down of PKCδ by PKCδ-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqα, phospholipase C (PLC)β1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCδ-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCδ and that PKCδ is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqα and PLCβ1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling. PMID:27379421

  16. PULMONARY GENE EXPRESSION PROFILES OF SPONTANEOUSLY HYPERTENSIVE RATS EXPOSED TO ENVIRONMENTAL TOBACCO SMOKE (ETS)

    EPA Science Inventory

    Global gene expression profile analysis can be utilized to derive molecular footprints to understand biochemical

    pathways implicated in the origin and progression of disease. Functional genomics efforts with tissue-specific focused

    genearray appears to be the most...

  17. ECG compression using Slantlet and lifting wavelet transform with and without normalisation

    NASA Astrophysics Data System (ADS)

    Aggarwal, Vibha; Singh Patterh, Manjeet

    2013-05-01

    This article analyses the performance of: (i) linear transform: Slantlet transform (SLT), (ii) nonlinear transform: lifting wavelet transform (LWT) and (iii) nonlinear transform (LWT) with normalisation for electrocardiogram (ECG) compression. First, an ECG signal is transformed using linear transform and nonlinear transform. The transformed coefficients (TC) are then thresholded using bisection algorithm in order to match the predefined user-specified percentage root mean square difference (UPRD) within the tolerance. Then, the binary look up table is made to store the position map for zero and nonzero coefficients (NZCs). The NZCs are quantised by Max-Lloyd quantiser followed by Arithmetic coding. The look up table is encoded by Huffman coding. The results show that the LWT gives the best result as compared to SLT evaluated in this article. This transform is then considered to evaluate the effect of normalisation before thresholding. In case of normalisation, the TC is normalised by dividing the TC by ? (where ? is number of samples) to reduce the range of TC. The normalised coefficients (NC) are then thresholded. After that the procedure is same as in case of coefficients without normalisation. The results show that the compression ratio (CR) in case of LWT with normalisation is improved as compared to that without normalisation.

  18. Normalising the Breast: Early Childhood Services Battling the Bottle and the Breast

    ERIC Educational Resources Information Center

    Duncan, Judith; Bartle, Carol

    2014-01-01

    Normalising practices as a tool for controlling the body and bodily processes have been well-documented using Foucault's theories, including debates around breastfeeding. In this article we explore how the ideas of "normalisation" of the bottle-feeding culture of infants in New Zealand early childhood settings has become the…

  19. Are We There Yet? Normalising CALL in the Context of Primary Languages in England

    ERIC Educational Resources Information Center

    Pazio, Monika

    2014-01-01

    The presence of technology in foreign education dates back to the 1960's. After over 50 years of research and practice, we are now moving towards discussion of identifying the end goal of integration that became known as normalisation (Bax, 2003). The majority of Computer-Assisted Language Learning (CALL) approaches and normalisation research is…

  20. Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.

    PubMed

    Gilbert, Jeffrey S; Gilbert, Sara A B; Arany, Marietta; Granger, Joey P

    2009-02-01

    Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; P<0.001), and fetal (2.35+/-0.05 g versus 1.76+/-0.08 g; P<0.001) and placental weight were decreased (0.47+/-0.04 g versus 0.58+/-0.03 g; P<0.01) in the RUPP compared with normal pregnant controls. Serum sEng (0.10+/-0.02 arbitrary pixel units [apu] versus 0.05+/-0.01 apu; P<0.05) and placental endoglin (4.7+/-2.3 apu versus 1.45+/-0.42 apu; P<0.05) were increased along with placental hypoxia inducible factor-1 alpha (1.42+/-0.25 apu versus 0.68+/-0.09 apu; P<0.05) expression in the RUPP versus the normal pregnant dams. Placental HO-1 (1.4+/-0.3 apu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy. PMID:19075097

  1. Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation.

    PubMed

    Saravanakumar, Murugesan; Raja, Boobalan; Manivannan, Jeganathan; Silambarasan, Thangarasu; Prahalathan, Pichavaram; Kumar, Subramanian; Mishra, Santosh Kumar

    2015-11-14

    In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling. PMID:26346559

  2. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

    PubMed

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action-studied by gene expression profiling in the liver-revealed deregulated genes from inflammatory and insulin signaling, AMP

  3. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    PubMed Central

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its “pleiotropic” effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action–studied by gene expression profiling in the liver–revealed deregulated genes from inflammatory and insulin signaling, AMP

  4. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... Renal artery stenosis is a narrowing or blockage of the arteries that supply blood to the kidneys. The most ...

  5. Hypertension - overview

    MedlinePlus Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  6. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... blood pressure to rise. Risk factors for atherosclerosis: High blood pressure Smoking Diabetes High cholesterol Heavy alcohol use Cocaine ...

  7. Ruscogenin exerts beneficial effects on monocrotaline-induced pulmonary hypertension by inhibiting NF-κB expression

    PubMed Central

    Zhu, Rong; Bi, Liqing; Kong, Hui; Xie, Weiping; Hong, Yongqing; Wang, Hong

    2015-01-01

    This study aims to examine the effect of ruscogenin on pulmonary arterial hypertension (PAH) and to determine the mechanism underlying this effect. We isolated pulmonary vascular smooth muscle cells (PVSMCs) from the pulmonary artery of the rats; the PVSMCs were cultured in vitro and then were treated with platelet-derived growth factor (PDGF), PDGF + ruscogenin, or PDGF + ruscogenin + parthenolide. We randomized Sprague-Dawley rats into five groups as follows: control group, PAH group, low-dose group, medium-dose group, and high-dose group; the rats in the low-, medium-, and high-dose groups received the vehicle and ruscogenin 0.1, 0.4, and 0.7 mg/kg, respectively, from day 1 to day 21 after injection of monocrotaline (MCT). We measured the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), and medial wall thickness of the pulmonary artery (PAWT). We examined the levels of the nuclear factor kappa B (NF-κB) protein by using immunohistochemistry and western blot analysis, and the mRNA levels of NF-κB in PVSMCs were evaluated using real-time polymerase chain reaction (PCR). The mPAP, RVSP, and PAWT and the protein and mRNA levels of NF-κB were significantly higher in the PAH model group than in the control group (P < 0.05). Ruscogenin induced a significant dose-dependent decrease in the mPAP, RVSP, and PAWT and in the NF-κB expression in the PAH group (P < 0.05), which suggests that ruscogenin will also exert dose-dependent effects on MCT-induced PAH through the inhibition of NF-κB. PMID:26722401

  8. Mizoribine Ameliorates Renal Injury and Hypertension along with the Attenuation of Renal Caspase-1 Expression in Aldosterone-Salt-Treated Rats

    PubMed Central

    Doi, Toshiki; Doi, Shigehiro; Nakashima, Ayumu; Ueno, Toshinori; Yokoyama, Yukio; Kohno, Nobuoki; Masaki, Takao

    2014-01-01

    Aldosterone-salt treatment induces not only hypertension but also extensive inflammation that contributes to fibrosis in the rat kidney. However, the mechanism underlying aldosterone-salt-induced renal inflammation remains unclear. Pyroptosis has recently been identified as a new type of cell death that is accompanied by the activation of inflammatory cytokines. We hypothesized that aldosterone-salt treatment could induce inflammation through pyroptosis and that mizoribine, an effective immunosuppressant, would ameliorate the renal inflammation that would otherwise cause renal fibrosis. Ten days after recovery from left uninephrectomy, rats were given drinking water with 1% sodium chloride. The animals were divided into three groups (n = 7 per group): (1) vehicle infusion group, (2) aldosterone infusion group, or (3) aldosterone infusion plus oral mizoribine group. Aldosterone-salt treatment increased the expression of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 and caspase-1, and also increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. However, the oral administration of mizoribine attenuated these alterations. Furthermore, mizoribine inhibited hypertension and renal fibrosis, and also attenuated the aldosterone-induced expression of serum/glucocorticoid-regulated kinase and α epithelial sodium channel. These results suggest that caspase-1 activation plays an important role in the development of inflammation induced by aldosterone-salt treatment and that it functions as an anti-inflammatory strategy that protects against renal injury and hypertension. PMID:24695748

  9. ASCAT Normalised Radar Backscatter At Full Measurement Resolution

    NASA Astrophysics Data System (ADS)

    Figa-Saldana, Julia; Anderson, Craig; Bonekamp, Hans; Duff, Colin; Santuari, Mirko; Wilson, Julian

    2013-12-01

    The Advanced Scatterometer (ASCAT) is a real aperture, vertical polarisation, C-band radar designed primarily to provide global ocean winds operationally [1] [2]. The main application of these data is the assimilation into numerical weather prediction models, but its dense coverage makes the data also extremely useful for direct use by operational weather forecasters in near real time. The basic measurement provided by the ASCAT is the Normalised Radar Cross Section (NRCS), for which other important applications have emerged in the recent years over land and sea ice areas, where it provides information on soil moisture, snow and sea ice parameters, such as ice age and drift. In particular with respect to soil moisture, ASCAT is currently used operationally in the context of data assimilation by several weather prediction centres and important steps are being taken for its specific use in hydrology applications. Three types of NRCS products are produced at EUMETSAT. The ‘SZO' and ‘SZR' products contain triplets of collocated averaged NRCS values on a regular grid of nodes along and across swath. The 'SZF' product contains geolocated NRCS values at full resolution for each of the beams. All products are distributed in near real time by EUMETSAT and are also available from the EUMETSAT Data Centre. We describe the latest version of the SZF product, which has been enhanced to make it easier to use and more compact. It contains now a regular grid of points with a spacing of around 6.25 km, which is consistent with the grid points in the SZO and SZR products. We also present an analysis of the full resolution data, showing example results that can be obtained when it is spatially averaged for specific applications.

  10. Effects of baicalin on collagen Ι and collagen ΙΙΙ expression in pulmonary arteries of rats with hypoxic pulmonary hypertension

    PubMed Central

    LIU, PANPAN; YAN, SHUANGQUAN; CHEN, MAYUN; CHEN, ALI; YAO, DAN; XU, XIAOMEI; CAI, XUEDING; WANG, LIANGXING; HUANG, XIAOYING

    2015-01-01

    The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for

  11. Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.

    PubMed

    Collister, John P; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C

    2014-01-01

    The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·- in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·- in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

  12. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  13. Hypertension in Malaysia

    PubMed Central

    Naing, Cho; Yeoh, Peng Nam; Wai, Victor Nyunt; Win, Ni Ni; Kuan, Lai Pei; Aung, Kyan

    2016-01-01

    Abstract This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia. The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable. Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%–35.8%) in 1996, 42.6% (37.5%–43.5%) in 2006, and 43.5% (40.4%–46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P < 0.001) and of 29% from 1996 to 2006 (P < 0.05), but only a small change of 1% from 2006 to 2011 (P = 0.6). For population ≥18 years, only a 1% increase in prevalence of hypertension occurred from the 2006 NHMS (32.2%) to the 2011 NHMS (32.7%) (P = 0.25). A relative increase of 13% occurred in those with primary education (P < 0.001) and a 15% increase was seen in those with secondary education (P < 0.001). The rate of increase in the prevalence of hypertension in the population with income level RM 3000–3999 was the highest (18%) during this period. In general, the older age group had higher prevalence of hypertension in the 2006 and 2011 NHMSs. The prevalence peaked at 74.1% among population aged 65 to 69 years in the 2011 NHMS. Both the proportion of awareness and the control of hypertension in Malaysia improved from 1996 to 2006. A change in the control of hypertension was 13% higher in women than in men. The findings suggest that

  14. ROMK expression remains unaltered in a mouse model of familial hyperkalemic hypertension caused by the CUL3Δ403-459 mutation.

    PubMed

    Murthy, Meena; Kurz, Thimo; O'Shaughnessy, Kevin M

    2016-07-01

    Familial hyperkalemic hypertension (FHHt) is a rare inherited form of salt-dependent hypertension caused by mutations in proteins that regulate the renal Na(+)-Cl(-) cotransporter NCC Mutations in four genes have been reported to cause FHHt including CUL3 (Cullin3) that encodes a component of a RING E3 ligase. Cullin-3 binds to WNK kinase-bound KLHL3 (the substrate recognition subunit of the ubiquitin ligase complex) to promote ubiquitination and proteasomal degradation of WNK kinases. Deletion of exon 9 from CUL3 (affecting residues 403-459, CUL3(Δ403-459)) causes a severe form of FHHt (PHA2E) that is recapitulated closely in a knock-in mouse model. The loss of functionality of CUL3(Δ403-459) and secondary accumulation of WNK kinases causes substantial NCC activation. This accounts for the hypertension in FHHt but the origin of the hyperkalemia is less clear. Hence, we explored the impact of CUL3(Δ403-459) on expression of the distal secretory K channel, ROMK, both in vitro and in vivo. We found that expressing wild-type but not the CUL3(Δ403-459) mutant form of CUL3 prevented the suppression of ROMK currents by WNK4 expressed in Xenopus oocytes. The mutant CUL3 protein was also unable to affect ROMK-EGFP protein expression at the surface of mouse M-1 cortical collecting duct (CCD) cells. The effects of CUL3 on ROMK expression in both oocytes and M-1 CCD cells was reduced by addition of the neddylation inhibitor, MLN4924. This confirms that neddylation is important for CUL3 activity. Nevertheless, in our knock-in mouse model expressing CUL3(Δ403-459) we could not show any alteration in ROMK expression by either western blotting whole kidney lysates or confocal microscopy of kidney sections. This suggests that the hyperkalemia in our knock-in mouse and human PHA2E subjects with the CUL3(Δ403-459) mutation is not caused by reduced ROMK expression in the distal nephron. PMID:27378813

  15. Resistant Hypertension.

    PubMed

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension. PMID:26935512

  16. Expression and Activation of STAT3 in the Astrocytes of Optic Nerve in a Rat Model of Transient Intraocular Hypertension

    PubMed Central

    Zhang, Shaodan; Li, Weiyi; Wang, Wenqian; Zhang, Samuel S.; Huang, Ping; Zhang, Chun

    2013-01-01

    Lamina cribosa, an astrocyte-rich region, is the origin of axonal degeneration in glaucomatous neuropathy. Astrocytes are particularly activated during optic nerve (ON) degeneration and are likely to contribute to the pathogenesis of glaucomatous optic neuropathy. Signalling mechanisms that regulate different aspects of astrocyte reactiviation in response to intraocular hypertensive injury are not well defined. Signal transducer and activator of transcription protein-3 (STAT3) is a transcription factor that participates in many biological processes and has been implicated as activator of reactive astrogliosis. In this study, we investigated the role of STAT3 in regulating the activation of astrocytes to transient intraocular hypertension in vivo by using a rat ocular hypertension model. ON astrocytes hypertrophy was observed early after intraocular hypertensive stress. Morphological changes in glial fibrillary acidic protein (GFAP) positive cells coupled with axon loss in the optic nerve was detected at day 7 after the injury. Nestin was significantly upregulated in ON astrocytes as early as day 2 post injury and kept elevated through post injury day 7. Phosphorylated STAT3 (pSTAT3) was markedly upregulated in ON astrocytes at post injury day 1, prior to the reactivation of ON astrocytes. These findings indicate that STAT3 signalling is involved in the initiation of astrocyte reactivation in optic nerve injury. PMID:23383263

  17. Malignant hypertension

    MedlinePlus

    ... Lippincott Williams & Wilkins; 2009:chap 89. Read More Acute kidney failure Alertness - decreased Angina Heart attack Preeclampsia Pulmonary edema Renovascular hypertension Seizures Stroke Update ...

  18. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 – 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism – Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  19. Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans

    PubMed Central

    Duraimani, Shanthi; Schneider, Robert H.; Randall, Otelio S.; Nidich, Sanford I.; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A.; Gaylord-King, Carolyn; Salerno, John W.; Fagan, John

    2015-01-01

    Background African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Methods Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Results Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. Conclusion In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP

  20. The importance of the selection of appropriate reference genes for gene expression profiling in adrenal medulla or sympathetic ganglia of spontaneously hypertensive rat.

    PubMed

    Vavřínová, A; Behuliak, M; Zicha, J

    2016-07-18

    Catecholaminergic system plays an important role in hypertension development. The available results on mRNA expression of catecholaminergic system genes in spontaneously hypertensive rats (SHR) are often contradictory. One of the possible causes might be the use of various reference genes as internal controls. In the present study, we searched for suitable reference genes in adrenal medulla or sympathetic ganglia of SHR and Wistar-Kyoto (WKY) rats, which would enable reliable comparison of mRNA expression between these two strains. The mRNA expression was measured by quantitative real-time PCR in adrenal medulla and superior cervical ganglia of 4-week-old or 24-week-old SHR and WKY rats. We evaluated 12 reference genes by three software tools (Normfinder, BestKeeper, geNorm) and compared them for the standardization of mRNA expression. Combination of reference genes Hprt1 and Ywhaz in adrenal medulla and Gapdh and 18S in sympathetic ganglia were chosen as the best ones. 18S was found as applicable reference gene in both tissues. We found many alterations in expression of catecholaminergic system genes in adrenal medulla and sympathetic ganglia of SHR. The usage of the most or the least stable reference gene as internal control changed results moderately in sympathetic ganglia but seriously in adrenal medulla. For example, tyrosine hydroxylase (Th) gene was underexpressed in adrenal medulla of adult SHR using the appropriate reference gene but unchanged after the standardization to the least stable reference gene. Our results indicate the importance of appropriate internal control. The suitability of reference genes should be checked again in the case of change in experimental conditions. PMID:27070752

  1. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    PubMed Central

    Berkban, Thewarid; Boonprom, Pattanapong; Bunbupha, Sarawoot; Umka Welbat, Jariya; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pakdeechote, Poungrat; Prachaney, Parichat

    2015-01-01

    The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks. L-NAME induced high systolic blood pressure (SBP) and increased heart rate (HR), hindlimb vascular resistance (HVR) and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg) prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability. PMID:26133972

  2. Alteration of Gene Expression Profile in Kidney of Spontaneously Hypertensive Rats Treated with Protein Hydrolysate of Blue Mussel (Mytilus edulis) by DNA Microarray Analysis.

    PubMed

    Feng, Junli; Dai, Zhiyuan; Zhang, Yanping; Meng, Lu; Ye, Jian; Ma, Xuting

    2015-01-01

    Marine organisms are rich sources of bioactive components, which are often reported to have antihypertensive effects. However, the underlying mechanisms have yet to be fully identified. The aim of this study was to investigate the antihypertensive effect of enzymatic hydrolysis of blue mussel protein (HBMP) in rats. Peptides with in vitro ACE inhibitory activity were purified from HBMP by ultrafiltration, gel filtration chromatography and reversed-phase high performance liquid chromatography. And the amino acid sequences of isolated peptides were estimated to be Val-Trp, Leu-Gly-Trp, and Met-Val-Trp-Thr. To study its in vivo action, spontaneously hypertensive rats (SHRs) were orally administration with high- or low-dose of HBMP for 28 days. Major components of the renin-angiotensin (RAS) system in serum of SHRs from different groups were analyzed, and gene expression profiling were performed in the kidney of SHRs, using the Whole Rat Genome Oligonucleotide Microarray. Results indicated although genes involved in RAS system were not significantly altered, those related to blood coagulation system, cytokine and growth factor, and fatty acids metabolism were remarkablely changed. Several genes which were seldom reported to be implicated in pathogenesis of hypertension also showed significant expression alterations after oral administration of HBMP. These data provided valuable information for our understanding of the molecular mechanisms that underlie the potential antihypertensive activities of HBMP, and will contribute towards increased value-added utilization of blue mussel protein. PMID:26517713

  3. WNK1-related Familial Hyperkalemic Hypertension results from an increased expression of L-WNK1 specifically in the distal nephron.

    PubMed

    Vidal-Petiot, Emmanuelle; Elvira-Matelot, Emilie; Mutig, Kerim; Soukaseum, Christelle; Baudrie, Véronique; Wu, Shengnan; Cheval, Lydie; Huc, Elizabeth; Cambillau, Michèle; Bachmann, Sebastian; Doucet, Alain; Jeunemaitre, Xavier; Hadchouel, Juliette

    2013-08-27

    Large deletions in the first intron of the With No lysine (K) 1 (WNK1) gene are responsible for Familial Hyperkalemic Hypertension (FHHt), a rare form of human hypertension associated with hyperkalemia and hyperchloremic metabolic acidosis. We generated a mouse model of WNK1-associated FHHt to explore the consequences of this intronic deletion. WNK1(+/FHHt) mice display all clinical and biological signs of FHHt. This phenotype results from increased expression of long WNK1 (L-WNK1), the ubiquitous kinase isoform of WNK1, in the distal convoluted tubule, which in turn, stimulates the activity of the Na-Cl cotransporter. We also show that the activity of the epithelial sodium channel is not altered in FHHt mice, suggesting that other mechanisms are responsible for the hyperkalemia and acidosis in this model. Finally, we observe a decreased expression of the renal outer medullary potassium channel in the late distal convoluted tubule of WNK1(+/FHHt) mice, which could contribute to the hyperkalemia. In summary, our study provides insights into the in vivo mechanisms underlying the pathogenesis of WNK1-mediated FHHt and further corroborates the importance of WNK1 in ion homeostasis and blood pressure. PMID:23940364

  4. Alteration of Gene Expression Profile in Kidney of Spontaneously Hypertensive Rats Treated with Protein Hydrolysate of Blue Mussel (Mytilus edulis) by DNA Microarray Analysis

    PubMed Central

    Feng, Junli; Dai, Zhiyuan; Zhang, Yanping; Meng, Lu; Ye, Jian; Ma, Xuting

    2015-01-01

    Marine organisms are rich sources of bioactive components, which are often reported to have antihypertensive effects. However, the underlying mechanisms have yet to be fully identified. The aim of this study was to investigate the antihypertensive effect of enzymatic hydrolysis of blue mussel protein (HBMP) in rats. Peptides with in vitro ACE inhibitory activity were purified from HBMP by ultrafiltration, gel filtration chromatography and reversed-phase high performance liquid chromatography. And the amino acid sequences of isolated peptides were estimated to be Val-Trp, Leu-Gly-Trp, and Met-Val-Trp-Thr. To study its in vivo action, spontaneously hypertensive rats (SHRs) were orally administration with high- or low-dose of HBMP for 28 days. Major components of the renin-angiotensin (RAS) system in serum of SHRs from different groups were analyzed, and gene expression profiling were performed in the kidney of SHRs, using the Whole Rat Genome Oligonucleotide Microarray. Results indicated although genes involved in RAS system were not significantly altered, those related to blood coagulation system, cytokine and growth factor, and fatty acids metabolism were remarkablely changed. Several genes which were seldom reported to be implicated in pathogenesis of hypertension also showed significant expression alterations after oral administration of HBMP. These data provided valuable information for our understanding of the molecular mechanisms that underlie the potential antihypertensive activities of HBMP, and will contribute towards increased value-added utilization of blue mussel protein. PMID:26517713

  5. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation. PMID:18769797

  6. Sensitivity-based operational mode shape normalisation: Application to a bridge

    NASA Astrophysics Data System (ADS)

    Parloo, E.; Cauberghe, B.; Benedettini, F.; Alaggio, R.; Guillaume, P.

    2005-01-01

    Recently, an innovative sensitivity-based technique was introduced for the normalisation of operational mode shapes purely on a basis of output-only data. The technique is based on the use of a controlled mass modification experiment and does not involve any analytical models. Moreover, it allows to extend the applicability of many modal analysis based applications towards the domain of in-operation modal testing. Previously, this method was successfully tested by means of experiments on various mechanical engineering structures. The focus of this contribution is the validation of the sensitivity-based normalisation technique on a civil structure. For this purpose, measurements were performed on a bridge.

  7. Hypertensive crisis.

    PubMed

    Rubenstein, E B; Escalante, C

    1989-07-01

    Hypertensive crisis is an acute emergency requiring aggressive management. Its incidence has decreased in recent years but still is prevalent in the medical community. From review of past and present treatment regimens, the following recommendations can be considered. (1) In the treatment of malignant hypertension with associated CHF, sodium nitroprusside is still an excellent agent. It has a rapid onset of action and blood pressure can be easily titrated. Nitroglycerin is also another agent that can be used in this situation. (2) In the treatment of malignant hypertension with associated aortic dissection, trimethophan camsylate is the preferred agent. An alternative choice is the combination of nitroprusside and labetalol. (3) In the treatment of malignant hypertension with associated myocardial ischemia, an excellent choice is nitroglycerin. Labetalol also should be considered in this situation. (4) In the treatment of hypertension during pregnancy, hydralazine is still a good choice. Labetalol has also been shown to be efficacious. (5) In the treatment of malignant hypertension with associated cerebral ischemia, the following drugs should be considered: nitroprusside, nitroglycerin, and labetalol. The most important attribute of these agents is that they are nonsedating and rapid in onset. (6) In the treatment of postoperative hypertension the choices best suited are labetalol, enalapril, nitroprusside, and nitroglycerin. These agents are rapid in onset and all can be administered intravenously. PMID:2670090

  8. Epidemiology and Genetics of Hypertension.

    PubMed

    Sarkar, Taposh; Singh, Narinder Pal

    2015-09-01

    The prevalence of hypertension is increasing in India as well as in the world. The average prevalence of hypertension in India is 25-30%. The median prevalence of total hypertension in 2009 was 37.6% in men and 40.1% in women in U.S. Hypertension is a major risk factor for majority of patients with cardiovascular, cerebrovascular and renal morbidity and mortality. Environmental factors as well as genetic factors account for regulation of blood pressure and its control. Understanding of genetic factor may not only help in recognising those at risk but also help in treatment. Discovering hypertension susceptibility genes would help recognizing those at risk for developing the disease before the expression of clinical symptoms. Genetic and epidemiological studies have suggested that essential hypertension is a polygenic and multifactorial disorder that results from genetic and/or environmental factors. In India awareness, treatment and control status of hypertension is low, with only half of the urban and a quarter of the rural hypertensive individuals being aware of its presence. In this review we have discussed epidemiology and genetics of hypertension, both the monogenic and polygenic forms. PMID:27608868

  9. Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCA-salt hypertension

    PubMed Central

    Banes, Amy KL; Watts, Stephanie W

    2003-01-01

    Background 5-hydroxytryptamine (5-HT)2B and 5-HT1B receptors are upregulated in arteries from hypertensive DOCA-salt rats and directly by mineralocorticoids. We hypothesized that increased 5-HT2B and 5-HT1B receptor density and contractile function would precede increased blood pressure in DOCA-high salt rats. We performed DOCA-salt time course (days 1, 3, 5 and 7) studies using treatment groups of: DOCA-high salt, DOCA-low salt, Sham and Sham-high salt rats. Results In isolated-tissue baths, DOCA-high salt aorta contracted to the 5-HT2B receptor agonist BW723C86 on day 1; Sham aorta did not contract. The 5-HT1B receptor agonist CP93129 had no effect in arteries from any group. On days 3, 5 and 7 CP93129 and BW723C86 contracted DOCA-high salt and Sham-high salt aorta; Sham and DOCA-low salt aorta did not respond. Western analysis of DOCA-high salt aortic homogenates revealed increased 5-HT2B receptor levels by day 3; 5-HT1B receptor density was unchanged. Aortic homogenates from the other groups showed unchanged 5-HT2B and 5-HT1B receptor levels. Conclusion These data suggest that functional changes of 5-HT2B but not 5-HT1B receptors may play a role in the development of DOCA-salt hypertension. PMID:12974983

  10. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  11. Hypertension screening

    NASA Technical Reports Server (NTRS)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  12. [Hypertensive retinopathy].

    PubMed

    Genevois, Olivier; Paques, Michel

    2010-01-20

    Acute hypertensive retinopathy should be distinguished from retinal arteriolosclerosis. The presence of microvascular abnormalities in the ocular fundus increases the risk of heart and/or brain attack. At the clinical level, the current classification of chronic hypertensive retinopathy is based on the long-term risk of stroke. In research, a great number of studies are focused on the predictive value of retinal vascular diameters related to the general micro- and macrovascular disease. PMID:20222306

  13. Does the Daily Choice Making of Adults with Intellectual Disability Meet the Normalisation Principle?

    ERIC Educational Resources Information Center

    Smith, Rosanne Burton; Morgan, Michaela; Davidson, John

    2005-01-01

    Background: This study examined whether daily choice availability for adults with intellectual disability was consistent with Nirje's (1973) normalisation principle. Method: Ratings of the daily choice availability of 59 people with intellectual disability in group homes and 198 individuals without intellectual disability in family homes were…

  14. "It's Just the Way It Is..." or Not? How Physical Education Teachers Categorise and Normalise Differences

    ERIC Educational Resources Information Center

    van Amsterdam, Noortje; Knoppers, Annelies; Claringbould, Inge; Jongmans, Marian

    2012-01-01

    This article explores how Dutch physical education (PE) teachers discursively construct body differences between students related to gender, (dis)ability and health. Our results show how disciplinary technologies of categorisation and normalisation are embedded in two distinct discourses that our participants used: the discourse of naturalness for…

  15. But It's Not All about the Sex: Mothering, Normalisation and Young Learning Disabled People

    ERIC Educational Resources Information Center

    Rogers, Chrissie

    2010-01-01

    This paper is about mothering, young learning disabled people, their sexualised and relationship lives and normalisation--not through the lens of the disabled person, but via a mothers perspective and theoretical discussion. As a mother who has a learning disabled daughter, a feminist and an academic my own mothering experience, my Ph.D. research…

  16. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  17. Systemic hypertension.

    PubMed

    Elliott, William J

    2007-04-01

    Hypertension is a growing public health problem worldwide. Only 37% of American hypertensives currently have their blood pressures controlled. Hypertension is traditionally diagnosed in the medical office, but both home and ambulatory blood pressure monitoring can help. Lifestyle modifications are recommended for everyone who has higher than "normal" blood pressure (<120/80 mm Hg). Voluminous clinical trial data support beginning drug therapy with low-dose chlorthalidone, unless the patient has a specific indication for a different drug. Additional drugs (typically in the sequence, angiotensin converting-enzyme inhibitor or angiotensin receptor blocker, calcium antagonist, beta-blocker, alpha-blocker, aldosterone antagonist, direct vasodilator, and centrally acting alpha(2)-agonist) can be added to achieve the blood pressure goal (usually <140/90 mm Hg, but <130/80 mm Hg for diabetics and those with chronic kidney disease). Special circumstances exist for treatment of hypertension in pregnancy, in childhood, in the elderly, and in both extremes of blood pressure (pre-hypertension or hypertensive emergencies). PMID:17398315

  18. Hypertensive emergencies.

    PubMed

    Murphy, C

    1995-11-01

    Hypertensive emergencies are uncommon and physiologically diverse. Consequently, it is difficult for most physicians to develop a familiarity with all the different hypertensive crises and with all drugs available for treating them (Table 4). Clinicians should not agonize over which is the perfect therapeutic agent for a particular emergency, but instead, they should focus on scrupulous monitoring and familiarize themselves with a few agents that will serve in most situations. Generally, these agents will be sodium nitroprusside and nitroglycerin. Vigilant neurologic monitoring is mandatory in all hypertensive emergencies. The early symptoms and signs of cerebral hypoperfusion can be vague and subtle, but if recognized, serious complications of therapy can be avoided. Remember, the patient may still be hypertensive. Avoid acute (during the first hour) reductions in MAP of more than 20% whenever possible; subsequent reductions should be gradual. In patients known to have markedly elevated ICP and who need acute reductions in their BP, serious consideration should be given to direct monitoring of the ICP so that CPP can be maintained within safe limits. In general, oral agents should not be used for the treatment of hypertensive emergencies. Intravenous Labetalol and intravenous nicardipine are not suitable for general use in hypertensive emergencies. In special situations (e.g., perioperative hypertension and subarachnoid hemorrhage), however, they may be employed. Their role may expand with further study. Trimethaphan may be superior to nitroprusside for hypertension complicated by elevated ICP or cerebral dysfunction. Realistically, most physicians will continue to use nitroprusside. Intense neurologic monitoring is more important than the specific agent used. Nitroglycerin is the agent of choice for acute ischemic heart disease complicated by severe hypertension; if it fails, use nitroprusside. For aortic dissection, the combination of nitroprusside and IV

  19. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    SciTech Connect

    Shao, Dongmin; Perros, Frédéric; Caramori, Gaetano; Meng, Chao; Dormuller, Peter; Chou, Pai-Chien; Church, Colin; Papi, Alberto; Casolari, Paolo; Welsh, David; Peacock, Andrew; Humbert, Marc; Adcock, Ian M.; Wort, Stephen J.

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  20. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  1. Diagnosing hypertension

    PubMed Central

    Gelfer, Mark; Dawes, Martin; Kaczorowski, Janusz; Padwal, Raj; Cloutier, Lyne

    2015-01-01

    Abstract Objective To highlight the 2015 Canadian Hypertension Education Program (CHEP) recommendations for the diagnosis and assessment of hypertension. Quality of evidence A systematic search was performed current to August 2014 by a Cochrane Collaboration librarian using the MEDLINE and PubMed databases. The search results were critically appraised by the CHEP subcommittee on blood pressure (BP) measurement and diagnosis, and evidence-based recommendations were presented to the CHEP Central Review Committee for independent review and grading. Finally, the findings and recommendations were presented to the Recommendations Task Force for discussion, debate, approval, and voting. The main recommendations are based on level II evidence. Main message Based on the most recent evidence, CHEP has made 4 recommendations in 2 broad categories for 2015 to improve BP measurement and the way hypertension is diagnosed. A strong recommendation is made to use electronic BP measurement in the office setting to replace auscultatory BP measurement. For patients with elevated office readings, CHEP is recommending early use of out-of-office BP measurement, preferably ambulatory BP measurement, in order to identify early in the process those patients with white-coat hypertension. Conclusion Improvements in diagnostic accuracy are critical to optimizing hypertension management in Canada. The annual updates provided by CHEP ensure that practitioners have up-to-date evidence-based information to inform practice. PMID:26564654

  2. [Portopulmonary hypertension].

    PubMed

    Halank, M; Miehlke, S; Kolditz, M; Hoeffken, G

    2005-07-01

    Patients with portal hypertension may develop pulmonary complications such as hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PPHT). PPHT is defined as elevated pulmonary pressure, elevated pulmonary vascular resistance, a normal pulmonary capillary wedge pressure, and portal hypertension in the absence of other known causes pulmonary hypertension. Various factors such as hyperdynamic circulation, volume overload, and circulating vasoactive mediators are suspected to be involved in the pathogenesis of PPHT. The prognosis of patients with severe PPHT is significantly reduced due to the risk of right heart failure. In patients with moderate to severe PPHT liver transplantation is associated with a significantly increased mortality. The chief symptom of PPHT may be dyspnoe in the presence of typical histomorphological alterations comparable with idiopathic pulmonary hypertension. Continuous intravenous application of prostacyclin is currently regarded as the treatment of choice for patients with severe PPHT. Inhaled prostacyclin or its analogue iloprost or oral treatment with the endothelin-receptor antagonist bosentan may be promising alternatives which should be further investigated in randomized controlled trials. PMID:16001350

  3. [Effect of chrysin on expression of NOX4 and NF-κB in right ventricle of monocrotaline-induced pulmonary arterial hypertension of rats].

    PubMed

    Li, Xian-wei; Guo, Bo; Shen, Yuan-yuan; Yang, Jie-ren

    2015-09-01

    The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation. PMID:26757549

  4. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    PubMed

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury. PMID:27194718

  5. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.

    PubMed

    Machnik, Agnes; Dahlmann, Anke; Kopp, Christoph; Goss, Jennifer; Wagner, Hubertus; van Rooijen, Nico; Eckardt, Kai-Uwe; Müller, Dominik N; Park, Joon-Keun; Luft, Friedrich C; Kerjaschki, Dontscho; Titze, Jens

    2010-03-01

    We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain

  6. NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives.

    PubMed

    Park, Joon-Young; Farrance, Iain K G; Fenty, Nicola M; Hagberg, James M; Roth, Stephen M; Mosser, David M; Wang, Min Qi; Jo, Hanjoong; Okazaki, Toshihiko; Brant, Steven R; Brown, Michael D

    2007-10-01

    In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage I hypertensive individuals before and after a 6-mo supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the (-94)NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity. PMID:17644577

  7. Increased Pyruvate Dehydrogenase Kinase 4 Expression in Lung Pericytes Is Associated with Reduced Endothelial-Pericyte Interactions and Small Vessel Loss in Pulmonary Arterial Hypertension.

    PubMed

    Yuan, Ke; Shao, Ning-Yi; Hennigs, Jan K; Discipulo, Marielle; Orcholski, Mark E; Shamskhou, Elya; Richter, Alice; Hu, Xinqian; Wu, Joseph C; de Jesus Perez, Vinicio A

    2016-09-01

    Reduced endothelial-pericyte interactions are linked to progressive small vessel loss in pulmonary arterial hypertension (PAH), but the molecular mechanisms underlying this disease remain poorly understood. To identify relevant gene candidates associated with aberrant pericyte behavior, we performed a transcriptome analysis of patient-derived donor control and PAH lung pericytes followed by functional genomics analysis. Compared with donor control cells, PAH pericytes had significant enrichment of genes involved in various metabolic processes, the top hit being PDK4, a gene coding for an enzyme that suppresses mitochondrial activity in favor of glycolysis. Given reports that link reduced mitochondrial activity with increased PAH cell proliferation, we hypothesized that increased PDK4 is associated with PAH pericyte hyperproliferation and reduced endothelial-pericyte interactions. We found that PDK4 gene and protein expression was significantly elevated in PAH pericytes and correlated with reduced mitochondrial metabolism, higher rates of glycolysis, and hyperproliferation. Importantly, reducing PDK4 levels restored mitochondrial metabolism, reduced cell proliferation, and improved endothelial-pericyte interactions. To our knowledge, this is the first study that documents significant differences in gene expression between human donor control and PAH lung pericytes and the link between mitochondrial dysfunction and aberrant endothelial-pericyte interactions in PAH. Comprehensive characterization of these candidate genes could provide novel therapeutic targets to improve endothelial-pericyte interactions and prevent small vessel loss in PAH. PMID:27456128

  8. Use of a pre-analysis osmolality normalisation method to correct for variable urine concentrations and for improved metabolomic analyses.

    PubMed

    Chetwynd, Andrew J; Abdul-Sada, Alaa; Holt, Stephen G; Hill, Elizabeth M

    2016-01-29

    Metabolomics analyses of urine have the potential to provide new information on the detection and progression of many disease processes. However, urine samples can vary significantly in total solute concentration and this presents a challenge to achieve high quality metabolomic datasets and the detection of biomarkers of disease or environmental exposures. This study investigated the efficacy of pre- and post-analysis normalisation methods to analyse metabolomic datasets obtained from neat and diluted urine samples from five individuals. Urine samples were extracted by solid phase extraction (SPE) prior to metabolomic analyses using a sensitive nanoflow/nanospray LC-MS technique and the data analysed by principal component analyses (PCA). Post-analysis normalisation of the datasets to either creatinine or osmolality concentration, or to mass spectrum total signal (MSTS), revealed that sample discrimination was driven by the dilution factor of urine rather than the individual providing the sample. Normalisation of urine samples to equal osmolality concentration prior to LC-MS analysis resulted in clustering of the PCA scores plot according to sample source and significant improvements in the number of peaks common to samples of all three dilutions from each individual. In addition, the ability to identify discriminating markers, using orthogonal partial least squared-discriminant analysis (OPLS-DA), was greatly improved when pre-analysis normalisation to osmolality was compared with post-analysis normalisation to osmolality and non-normalised datasets. Further improvements for peak area repeatability were observed in some samples when the pre-analysis normalisation to osmolality was combined with a post-analysis mass spectrum total useful signal (MSTUS) or MSTS normalisation. Future adoption of such normalisation methods may reduce the variability in metabolomics analyses due to differing urine concentrations and improve the discovery of discriminating metabolites

  9. Expressed racial identity and hypertension in a telephone survey sample from Toronto and Vancouver, Canada: do socioeconomic status, perceived discrimination and psychosocial stress explain the relatively high risk of hypertension for Black Canadians?

    PubMed Central

    2012-01-01

    Introduction Canadian research on racial health inequalities that foregrounds socially constructed racial identities and social factors which can explain consequent racial health inequalities is rare. This paper adopts a social typology of salient racial identities in contemporary Canada, empirically documents consequent racial inequalities in hypertension in an original survey dataset from Toronto and Vancouver, Canada, and then attempts to explain the inequalities in hypertension with information on socioeconomic status, perceived experiences with institutionalized and interpersonal discrimination, and psychosocial stress. Methods Telephone interviews were conducted in 2009 with 706 randomly selected adults living in the City of Toronto and 838 randomly selected adults living in the Vancouver Census Metropolitan Area. Bivariate analyses and logistic regression modeling were used to examine relationships between racial identity, hypertension, socio-demographic factors, socioeconomic status, perceived discrimination and psychosocial stress. Results The Black Canadians in the sample were the most likely to report major and routine discriminatory experiences and were the least educated and the poorest. Black respondents were significantly more likely than Asian, South Asian and White respondents to report hypertension controlling for age, immigrant status and city of residence. Of the explanatory factors examined in this study, only educational attainment explained some of the relative risk of hypertension for Black respondents. Most of the risk remained unexplained in the models. Conclusions Consistent with previous Canadian research, socioeconomic status explained a small portion of the relatively high risk of hypertension documented for the Black respondents. Perceived experiences of discrimination both major and routine and self-reported psychosocial stress did not explain these racial inequalities in hypertension. Conducting subgroup analyses by gender

  10. Unsupervised color normalisation for H and E stained histopathology image analysis

    NASA Astrophysics Data System (ADS)

    Celis, Raúl; Romero, Eduardo

    2015-12-01

    In histology, each dye component attempts to specifically characterise different microscopic structures. In the case of the Hematoxylin-Eosin (H&E) stain, universally used for routine examination, quantitative analysis may often require the inspection of different morphological signatures related mainly to nuclei patterns, but also to stroma distribution. Nevertheless, computer systems for automatic diagnosis are often fraught by color variations ranging from the capturing device to the laboratory specific staining protocol and stains. This paper presents a novel colour normalisation method for H&E stained histopathology images. This method is based upon the opponent process theory and blindly estimates the best color basis for the Hematoxylin and Eosin stains without relying on prior knowledge. Stain Normalisation and Color Separation are transversal to any Framework of Histopathology Image Analysis.

  11. Resonant-state-expansion Born approximation with a correct eigen-mode normalisation

    NASA Astrophysics Data System (ADS)

    Doost, M. B.

    2016-08-01

    The Born approximation (Born 1926 Z. Phys. 38 802) is a fundamental result in physics, it allows the calculation of weak scattering via the Fourier transform of the scattering potential. As was done by previous authors (Ge et al 2014 New J. Phys. 16 113048) the Born approximation is extended by including in the formula the resonant-states (RSs) of the scatterer. However in this study unlike previous studies the included eigen-modes are correctly normalised with dramatic positive consequences for the accuracy of the method. The normalisation of RSs used in the previous RS expansion Born approximation or resonant-state expansion (RSE) Born approximation made in Ge et al (2014 New J. Phys. 16 113048) has been shown to be numerically unstable in Muljarov et al (2014 arXiv:1409.6877) and by analytics here. The RSs of the system can be calculated using my recently discovered RSE perturbation theory for dispersive electrodynamic scatterers (Muljarov et al 2010 Europhys. Lett. 92 50010; Doost et al 2012 Phys. Rev. A 85 023835; Doost et al 2013 Phys. Rev. A 87 043827; Armitage et al 2014 Phys. Rev. A 89; Doost et al 2014 Phys. Rev. A 90 013834) and normalised correctly to appear in spectral Green's functions and hence the RSE Born approximation via the flux-volume normalisation which I recently rigorously derived in Armitage et al (2014 Phys. Rev. A 89), Doost et al (2014 Phys. Rev. A 90 013834), Doost (2016 Phys. Rev. A 93 023835). In the case of effectively one-dimensional systems I find a RSE Born approximation alternative to the scattering matrix method.

  12. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have it, the blood ... heart has to work harder to pump the blood through. Over time, your heart weakens and ... of PH include Shortness of breath during routine activity, such ...

  13. Portopulmonary hypertension.

    PubMed

    Lv, Yong; Han, Guohong; Fan, Daiming

    2016-07-01

    Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non-specific, patients should be actively screened for the presence of PoPH. Two-dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. PMID:27002212

  14. Pulmonary Hypertension

    MedlinePlus

    ... Anticoagulants (blood-thinning medicine) Calcium channel blockers Diuretics (water pills) Digoxin Your doctor will decide what type of medicine is right for you. In some cases, people who have pulmonary hypertension need surgical treatment. Surgical treatment options include a lung transplant and ...

  15. Hypertensive leucocytosis.

    PubMed

    Rajkumari, Rolinda; Laishram, Deben; Thiyam, Joshna; Javan, Ng

    2013-04-01

    There are studies showing association of high WBC count with the higher incidence of hypertension though a few are done in the Indian population. The present study was conducted with the view to find any significant increase in total leucocyte count and differential leucocyte count in hypertensive patient Twenty-seven hypertensives with 12 males and 15 females and 27 age and sex matched control subjects (normotensive) were studied. Hypertension was defined when the systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or history of taking antihypertensive medicine. Three blood pressure recordings at an interval of 2 minutes were taken after the patient was made to sit for 30 minutes with a standard mercury sphygmomanometer in the left arm. The disappearance of sound was used for diastolic blood pressure. Blood was drawn into EDTA containing vials. Two separate counts were performed: First for total leucocyte count (TLC) and second for determination of percentage of polymorphonuclear cells. For the TLC, 0.5 part of blood mixed with 10 part of Turk's fluid followed by counting of leucocyte in a counting chamber under light microscope. The percentage of polymorphonuclear leucocyte was performed on a slide after making the slide and staining it with Leishman's stain. The erythrocyte sedimentation rate (ESR) was performed using Wintrobe's methods. The first 1 hour reading on the Wintrobe's tube was taken for analysis. The total leucocyte count (TLC) for the study group as compared to the controls were 7413.70 +/- 735.45 cells/cmm and 5236.30 +/- 528.77 cells/ cmm which was statistically significant. The mean percentage neutrophils were 62.04 +/- 4.99 for study group and 53.00 +/- 3.44 for the controls; the mean percentage lymphocytes for the study group and the controls were 34.37 +/- 4.55 and 39.11 +/- 4.40 respectively. Both the mean percentage neutrophils and lymphocytes showed significant differences. The mean erythrocyte sedimentation rate (ESR) also showed

  16. Diagnostic classification, viral sexually transmitted infections and discourses of femininity: limits of normalisation to erase stigma.

    PubMed

    Cook, Catherine

    2013-06-01

    Clinicians in the field of women's sexual health typically classify the two most common viral sexually transmitted infections (STIs), the human papilloma virus and the herpes simplex virus, as relatively innocuous infections. Teaching interventions include 'normalising' adult sexual activity and the epidemiological ordinariness of infection. Normalising is intended to disarm the potential stigma of the diagnosis. In this study, in-depth email interviews were conducted with 26 women with a viral STI diagnosis and 12 sexual health clinicians. Data were analysed thematically using a feminist, poststructuralist approach. Normalising is contextualised as an example of the workings of western philosophical thought whereby dualistic classifications privilege certain terms and subordinate other terms. In this instance, the relative medical normalcy of viral STIs is given primacy compared to the social abnormality experienced by women. Although these viral STIs infect women and men, this research concentrates on women's learning about viral STIs. For women, beliefs about femininity, sexuality, health, morality and responsibility influence effects of a viral STI diagnosis. These discourses are clinically significant because beliefs that specifically link to ideas about how to be a woman are overlooked when clinicians devise educational interventions. PMID:22333002

  17. Statistical mapping of maize bundle intensity at the stem scale using spatial normalisation of replicated images.

    PubMed

    Legland, David; Devaux, Marie-Françoise; Guillon, Fabienne

    2014-01-01

    The cellular structure of plant tissues is a key parameter for determining their properties. While the morphology of cells can easily be described, few studies focus on the spatial distribution of different types of tissues within an organ. As plants have various shapes and sizes, the integration of several individuals for statistical analysis of tissues distribution is a difficult problem. The aim of this study is to propose a method that quantifies the average spatial organisation of vascular bundles within maize stems, by integrating information from replicated images. In order to compare observations made on stems of different sizes and shapes, a spatial normalisation strategy was used. A model of average stem contour was computed from the digitisation of several stem slab images. Point patterns obtained from individual stem slices were projected onto the average stem to normalise them. Group-wise analysis of the spatial distribution of vascular bundles was applied on normalised data through the construction of average intensity maps. A quantitative description of average bundle organisation was obtained, via a 3D model of bundle distribution within a typical maize internode. The proposed method is generic and could easily be extended to other plant organs or organisms. PMID:24622152

  18. Statistical Mapping of Maize Bundle Intensity at the Stem Scale Using Spatial Normalisation of Replicated Images

    PubMed Central

    Legland, David; Devaux, Marie-Françoise; Guillon, Fabienne

    2014-01-01

    The cellular structure of plant tissues is a key parameter for determining their properties. While the morphology of cells can easily be described, few studies focus on the spatial distribution of different types of tissues within an organ. As plants have various shapes and sizes, the integration of several individuals for statistical analysis of tissues distribution is a difficult problem. The aim of this study is to propose a method that quantifies the average spatial organisation of vascular bundles within maize stems, by integrating information from replicated images. In order to compare observations made on stems of different sizes and shapes, a spatial normalisation strategy was used. A model of average stem contour was computed from the digitisation of several stem slab images. Point patterns obtained from individual stem slices were projected onto the average stem to normalise them. Group-wise analysis of the spatial distribution of vascular bundles was applied on normalised data through the construction of average intensity maps. A quantitative description of average bundle organisation was obtained, via a 3D model of bundle distribution within a typical maize internode. The proposed method is generic and could easily be extended to other plant organs or organisms. PMID:24622152

  19. Normalisation process theory: a framework for developing, evaluating and implementing complex interventions

    PubMed Central

    2010-01-01

    Background The past decade has seen considerable interest in the development and evaluation of complex interventions to improve health. Such interventions can only have a significant impact on health and health care if they are shown to be effective when tested, are capable of being widely implemented and can be normalised into routine practice. To date, there is still a problematic gap between research and implementation. The Normalisation Process Theory (NPT) addresses the factors needed for successful implementation and integration of interventions into routine work (normalisation). Discussion In this paper, we suggest that the NPT can act as a sensitising tool, enabling researchers to think through issues of implementation while designing a complex intervention and its evaluation. The need to ensure trial procedures that are feasible and compatible with clinical practice is not limited to trials of complex interventions, and NPT may improve trial design by highlighting potential problems with recruitment or data collection, as well as ensuring the intervention has good implementation potential. Summary The NPT is a new theory which offers trialists a consistent framework that can be used to describe, assess and enhance implementation potential. We encourage trialists to consider using it in their next trial. PMID:20961442

  20. [Expression of Catechol-O-Methyltransferase (Comt), Mineralocorticoid Receptor (Mlr), and Epithelial Sodium Channel (ENaC) Genes in Kidneys of Hypertensive ISIAH Rats at Rest and during Response to Stress].

    PubMed

    Abramova, T O; Smolenskaya, S E; Antonov, E V; Redina, O E; Markel, A L

    2016-02-01

    Emotional stress plays a significant role in the processes of the development of arterial hypertension, especially in the presence of genetic predisposition. The origin and maintenance of hypertensive status during stress development can be activated by the sympathetic nervous system. An increase in sympathetic stimulation can, in turn, result in a change in the functions of kidneys, which provide fluid and electrolyte balance of the organism. A comparative study of the mRNA expression level of catechol-o-methyltransferase (Comt), mineralocorticoid receptor (Mlr), and β-subunit of epithelial sodium channel (β-ENaC) genes was conducted on the kidneys of hypertensive ISIAH rats and normotensive WAG rats at rest and after the effect of emotional stress. The discovered changes in the expression level of the selected genes confirm their involvement in increased sympathetic stimulation of the kidney, along with changes in the function of kidney regulation of fluid and electrolyte balance, which is an important factor of the development of sustained hypertension in the ISIAH rats strain. PMID:27215035

  1. Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat

    PubMed Central

    2014-01-01

    Background The etiology of the metabolic syndrome is complex, and is determined by the interplay of both genetic and environmental factors. The present study was designed to identify genes and proteins in the adipose tissues with altered expression in the spontaneously hypertensive/NIH –corpulent rat, SHR/NDmcr-cp (CP) and to find possible molecular targets associated with the pathogenesis or progression of obesity related to the metabolic syndrome. Methods We extracted RNAs and proteins from the epididymal adipose tissues in CP, SHR/Lean (Lean), and Wistar Kyoto (WKY) rats and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). Results The results showed different mRNA and protein expression levels in the adipose tissue: oligo DNA microarray identified 33 genes that were significantly (P < 0.01) up-regulated and 17 genes significantly down-regulated in CP compared with WKY and Lean rats at both 6 and 25 weeks of age. The affected genes-proteins were associated with lipolytic enzymes stimulated by peroxisome proliferator-activated receptor (PPAR) signaling. Further analysis using the 2D-DIGE connected with MALDI-TOF/TOF analysis, the expression of monoglyceride lipase (MGLL) was significantly up-regulated and that of carboxylesterase 3 (CES3) was significantly down-regulated in 6- and 25-week-old CP compared with age-matched control (WKY and Lean rats). Conclusions Our results suggest the possible involvement of proteins associated with adipocyte lipolysis in obesity related to the metabolic syndrome. PMID:24468282

  2. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  3. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  4. Hypertension Subtypes among Hypertensive Patients in Ibadan

    PubMed Central

    Salako, Babatunde L.; Ogunniyi, Adesola; Cooper, Richard S.

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%) and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus 6.2%) was higher among males (P = 0.048). Female subjects were more obese (P < 0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations. PMID:25389499

  5. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    PubMed

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction. PMID:26806799

  6. Peripheral blood B lymphocytes derived from patients with idiopathic pulmonary arterial hypertension express a different RNA pattern compared with healthy controls: a cross sectional study

    PubMed Central

    Ulrich, Silvia; Taraseviciene-Stewart, Laima; Huber, Lars C; Speich, Rudolf; Voelkel, Norbert

    2008-01-01

    Background Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and still incurable disease. Research of IPAH-pathogenesis is complicated by the lack of a direct access to the involved tissue, the human pulmonary vasculature. Various auto-antibodies have been described in the blood of patients with IPAH. The purpose of the present work was therefore to comparatively analyze peripheral blood B lymphocyte RNA expression characteristics in IPAH and healthy controls. Methods Patients were diagnosed having IPAH according to WHO (mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary occlusion pressure ≤ 15 mmHg, absence of another explaining disease). Peripheral blood B-lymphocytes of patients and controls were immediately separated by density gradient centrifugation and magnetic beads for CD19. RNA was thereafter extracted and analyzed by the use of a high sensitivity gene chip (Affymetrix HG-U133-Plus2) able to analyze 47000 transcripts and variants of human genes. The array data were analyzed by two different softwares, and up-and down-regulations were defined as at least 1.3 fold with standard deviations smaller than fold-changes. Results Highly purified B-cells of 5 patients with IPAH (mean pulmonary artery pressure 51 ± 13 mmHg) and 5 controls were analyzed. Using the two different analyzing methods we found 225 respectively 128 transcripts which were up-regulated (1.3–30.7 fold) in IPAH compared with healthy controls. Combining both methods, there were 33 overlapping up-regulated transcripts and no down-regulated B-cell transcripts. Conclusion Patients with IPAH have a distinct RNA expression profile of their peripheral blood B-lymphocytes compared to healthy controls with some clearly up-regulated genes. Our finding suggests that in IPAH patients B cells are activated. PMID:18269757

  7. Increase in caveolae and caveolin-1 expression modulates agonist-induced contraction and store- and receptor-operated Ca(2+) entry in pulmonary arteries of pulmonary hypertensive rats.

    PubMed

    Jiao, Hai-Xia; Mu, Yun-Ping; Gui, Long-Xin; Yan, Fu-Rong; Lin, Da-Cen; Sham, James S K; Lin, Mo-Jun

    2016-09-01

    Caveolin-1 (Cav-1) is a major component protein associated with caveolae in the plasma membrane and has been identified as a regulator of store-operated Ca(2+) entry (SOCE) and receptor-operated Ca(2+) entry (ROCE). However, the contributions of caveolae/Cav-1 of pulmonary arterial smooth muscle cells (PASMCs) to the altered Ca(2+) signaling pathways in pulmonary arteries (PAs) during pulmonary hypertension (PH) have not been fully characterized. The present study quantified caveolae number and Cav-1 expression, and determined the effects of caveolae disruption on ET-1, cyclopiazonic acid (CPA) and 1-Oleoyl-2-acetyl-glycerol (OAG)-induced contraction in PAs and Ca(2+) influx in PASMCs of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH rats. We found that the number of caveolae, and the Cav-1 mRNA and protein levels were increased significantly in PASMCs in both PH models. Disruption of caveolae by cholesterol depletion with methyl-β-cyclodextrin (MβCD) significantly inhibited the contractile response to ET-1, CPA and OAG in PAs of control rats. ET-1, SOCE and ROCE-mediated contractile responses were enhanced, and their susceptibility to MβCD suppression was potentiated in the two PH models. MβCD-induced inhibition was reversed by cholesterol repletion. Introduction of Cav-1 scaffolding domain peptide to mimic Cav-1 upregulation caused significant increase in CPA- and OAG-induced Ca(2+) entry in PASMCs of control, CH and MCT-treated groups. Our results suggest that the increase in caveolae and Cav-1 expression in PH contributes to the enhanced agonist-induced contraction of PA via modulation of SOCE and ROCE; and targeting caveolae/Cav-1 in PASMCs may provide a novel therapeutic strategy for the treatment of PH. PMID:27311393

  8. A Study of the Effects of Exercise on the Urinary Metabolome Using Normalisation to Individual Metabolic Output

    PubMed Central

    Daskalaki, Evangelia; Blackburn, Gavin; Kalna, Gabriela; Zhang, Tong; Anthony, Nahoum; Watson, David G.

    2015-01-01

    Aerobic exercise, in spite of its multi-organ benefit and potent effect on the metabolome, has yet to be investigated comprehensively via an untargeted metabolomics technology. We conducted an exploratory untargeted liquid chromatography mass spectrometry study to investigate the effects of a one-h aerobic exercise session in the urine of three physically active males. Individual urine samples were collected over a 37-h protocol (two pre-exercise and eight post-exercise). Raw data were subjected to a variety of normalization techniques, with the most effective measure dividing each metabolite by the sum response of that metabolite for each individual across the 37-h protocol expressed as a percentage. This allowed the metabolite responses to be plotted on a normalised scale. Our results highlight significant metabolites located in the following systems: purine pathway, tryptophan metabolism, carnitine metabolism, cortisol metabolism, androgen metabolism, amino acid oxidation, as well as metabolites from the gastrointestinal microbiome. Many of the significant changes observed in our pilot investigation mirror previous research studies, of various methodological designs, published within the last 15 years, although they have never been reported at the same time in a single study. PMID:25734341

  9. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    SciTech Connect

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  10. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  11. Hypertension and Spina Bifida

    MedlinePlus

    SBA National Resource Center: 800-621-3141 Hypertension A disease that often goes undetected. What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of ...

  12. What Causes Pulmonary Hypertension?

    MedlinePlus

    ... from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... different types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the ...

  13. Hormones and Hypertension

    MedlinePlus

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  14. Gene Expression Profiles of Peripheral Blood Mononuclear Cells Reveal Transcriptional Signatures as Novel Biomarkers for Cardiac Remodeling in Rats with Aldosteronism and Hypertensive Heart Disease

    PubMed Central

    Gerling, Ivan C.; Ahokas, Robert A.; Kamalov, German; Zhao, Wenyuan; Bhattacharya, Syamal K.; Sun, Yao; Weber, Karl T.

    2013-01-01

    Objectives In searching for a noninvasive surrogate tissue having mimicry with the prooxidant/-proinflammatory hypertensive heart disease (HHD) phenotype, we turned to peripheral blood mononuclear cells (PBMC). We tested whether iterations in [Ca2+]i, [Zn2+]i and oxidative stress in cardiomyocytes and PBMC would complement each other eliciting similar shifts in gene expression profiles in these tissues demonstrable during preclinical (wk 1) and pathologic (wk 4) stages of aldosterone/salt treatment (ALDOST). Background Inappropriate neurohormonal activation contributes to pathologic remodeling of myocardium in HHD associated with aldosteronism. In rats receiving chronic ALDOST, evidence of reparative fibrosis replacing necrotic cardiomyocytes and coronary vasculopathy appears at wk 4 associated with the induction of oxidative stress by mitochondria that overwhelms endogenous, largely Zn2+-based, antioxidant defenses. Biomarker-guided prediction of risk prior to the appearance of cardiac pathology would prove invaluable. Methods In PBMC and cardiomyocytes, quantitation of cytoplasmic free Ca2+ and Zn2+, H2O2 and 8-iosprostane levels, as well as isolation of RNA and gene expression, together with statistical and clustering analyses, and confirmation of genes by in situ hybridization and RT-PCR, were performed. Results Compared to controls, at wk 1 and 4 ALDOST, we found comparable: increments in [Ca2+]i, [Zn2+]i and 8-isoprotane coupled to increased H2O2 production in cardiac mitochondria and PBMC, together with the common networks of expression profiles dominated by genes involved in oxidative stress, inflammation and repair. These included three central Ingenuity pathway-linked genes: p38MAPK, a stress-responsive protein; NFκB, a redox-sensitive transcription factor and a proinflammatory cascade it regulates; and TGF-β1, a fibrogenic cytokine involved in tissue repair. Conclusions Significant overlapping demonstrated in the molecular mimicry of PBMC and

  15. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

    PubMed Central

    Galambos, Csaba; Minic, Angela D.; Bush, Douglas; Nguyen, Dominique; Dodson, Blair; Seedorf, Gregory; Abman, Steven H.

    2016-01-01

    Background and Aims Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. Methods Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. Results The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. Conclusions We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and

  16. Essential Hypertension vs. Secondary Hypertension Among Children

    PubMed Central

    Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E.; Barratt, Michelle S.; Hecht, Jacqueline T.; Milewicz, Diane M.; Boerwinkle, Eric

    2015-01-01

    BACKGROUND The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”) from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3–17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08–19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. PMID:24842390

  17. [Hypertensive emergencies and urgencies].

    PubMed

    Reingardiene, Dagmara

    2005-01-01

    Hypertension is one of the most common medical problems affecting approximately 1 billion individuals worldwide. Severe hypertension that is a potentially life-threatening condition refers to a hypertensive crisis. Severe hypertension is further classified into hypertensive emergencies or hypertensive urgencies. Hypertensive emergency refers to a severe hypertension that is associated with new or progressive end-organ damage. In these clinical situations, blood pressure should be reduced immediately to prevent or minimize organ dysfunction. Hypertensive urgency refers to severe hypertension without evidence of new or worsening end-organ injury. Blood pressure can be lowered less rapidly in this condition. In this review article it is discussed about clinical assessment of patients under these conditions, evaluating neurological, cardiovascular, renal end-organ damage; how much blood pressure should be lowered, which medication should be used to lower blood pressure, treating hypertensive emergencies and urgencies; and management of specific conditions (acute intracranial events, acute left ventricular dysfunction etc). PMID:15998994

  18. Non/infectious corporealities: tensions in the biomedical era of 'HIV normalisation'.

    PubMed

    Persson, Asha

    2013-09-01

    In the contemporary HIV epidemic, antiretroviral treatments are increasingly considered so effective at viral suppression that they render people with HIV sexually non-infectious. With its radical implications for global HIV prevention, this emerging paradigm is invested with the potential to turn the epidemic around and to 'normalise' one of the most feared infectious diseases in history, thus echoing wider trends of 'biomedicalisation'. What remains unexamined is whether this paradigm shift will bring about a parallel shift in the embodied experiences of being HIV-positive. This article explores the nascent trajectory from infectious to non-infectious corporeality against the backdrop of the discursive history of HIV, with particular focus on the landmark Swiss Consensus Statement, and in the context of research with heterosexuals with HIV in Australia. In-depth interviews revealed that HIV corporeality was not a stable, homogenised experience across participants and time, nor did it simply follow medical discourses. Instead, HIV corporeality emerged as a contingent set of tensions between conflicting discourses of infectiousness that were negotiated and made sense of within situated and embodied life histories. These findings pose challenges to the imperative of HIV normalisation and the related tendency in HIV prevention to universalise the notion of 'infectiousness'. PMID:23278343

  19. Dual targeting of Angiopoetin-2 and VEGF potentiates effective vascular normalisation without inducing empty basement membrane sleeves in xenograft tumours

    PubMed Central

    Coutelle, O; Schiffmann, L M; Liwschitz, M; Brunold, M; Goede, V; Hallek, M; Kashkar, H; Hacker, U T

    2015-01-01

    Background: Effective vascular normalisation following vascular endothelial growth factor (VEGF) inhibition is associated with endothelial cell regression leaving empty basement membrane sleeves (BMS). These long-lived BMS permit the rapid regrowth of tumour vasculature upon treatment cessation and promote resistance to VEGF-targeting drugs. Previous attempts at removing BMS have failed. Angiopoietin-2 (Ang2) is a vascular destabilizing factor that antagonises normalisation. We hypothesised that Ang2 inhibition could permit vascular normalisation at significantly reduced doses of VEGF inhibition, avoiding excessive vessel regression and the formation of empty BMS. Methods: Mice xenografted with human colorectal cancer cells (LS174T) were treated with low (0.5 mg kg−1) or high (5 mg kg−1) doses of the VEGF-targeting antibody bevacizumab with or without an Ang2 blocking peptibody L1-10. Tumour growth, BMS formation and normalisation parameters were examined including vessel density, pericyte coverage, adherence junctions, leakiness, perfusion, hypoxia and proliferation. Results: Dual targeting of VEGF and Ang2 achieved effective normalisation at only one-tenth of the dose required with bevacizumab alone. Pericyte coverage, vascular integrity, adherence junctions and perfusion as prerequisites for improved access of chemotherapy were improved without inducing empty BMS that facilitate rapid vascular regrowth. Conclusions: Dual targeting of VEGF and Ang2 can potentiate the effectiveness of VEGF inhibitors and avoid the formation of empty BMS. PMID:25562438

  20. Hypertensive Emergencies in Pregnancy.

    PubMed

    Olson-Chen, Courtney; Seligman, Neil S

    2016-01-01

    The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders. PMID:26600442

  1. Heat stress proteins in hypertension

    SciTech Connect

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-03-05

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46/sup 0/C during 5 min in a hot water bath. The cells were then labeled with (/sup 75/Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension.

  2. HNF1 AND HYPERTENSIVE NEPHROPATHY

    PubMed Central

    Dmitrieva, Renata I.; Hinojos, Cruz A.; Boerwinkle, Eric; Braun, Michael C.; Fornage, Myriam; Doris, Peter A.

    2009-01-01

    Hypertension in SHR is associated with renal redox stress and we hypothesized that nephropathy arises in SHR-A3 from altered capacity to mitigate redox stress compared with nephropathy-resistant SHR lines. We measured renal expression of redox genes in distinct lines of the spontaneously hypertensive rat (SHR-A3, SHR-B2, SHR-C) and the normotensive WKY strain. The SHR lines differ in either resisting (SHR-B2, SHR-C) or experiencing hypertensive nephropathy (SHR-A3). Immediately prior to the emergence of hypertensive renal injury expression of redox genes in SHR-A3 was profoundly altered compared with the injury-resistant SHR lines and WKY. This change appeared to arise in anti-oxidant genes where 16 of 28 were expressed at 34.3% of the level in the reference strain (WKY). No such change was observed in the injury-resistant SHR lines. We analyzed occurrence of transcription factor matrices (TFM) in the promoters of the down-regulated antioxidant genes. In these genes, the HNF1 TFM was found to be nearly twice as likely to be present and the overall frequency of HNF1 sites was nearly 5 times higher, compared with HNF1 TFMs in anti-oxidant genes that were not down-regulated. We identified 35 other (non-redox) renal genes regulated by HNF1. These were also significantly down-regulated in SHR-A3, but not in SHR-B2 or SHR-C. Finally, expression of genes that comprise HNF1 (Tcf1, Tcf2 and Dcoh) was also down-regulated in SHR-A3. The present experiments uncover a major change in transcriptional control by HNF1 that affects redox and other genes and precedes emergence of hypertensive renal injury. PMID:18443232

  3. The normalisation of terror: the response of Israel's stock market to long periods of terrorism.

    PubMed

    Peleg, Kobi; Regens, James L; Gunter, James T; Jaffe, Dena H

    2011-01-01

    Man-made disasters such as acts of terrorism may affect a society's resiliency and sensitivity to prolonged physical and psychological stress. The Israeli Tel Aviv stock market TA-100 Index was used as an indicator of reactivity to suicide terror bombings. After accounting for factors such as world market changes and attack severity and intensity, the analysis reveals that although Israel's financial base remained sensitive to each act of terror across the entire period of the Second Intifada (2000-06), sustained psychological resilience was indicated with no apparent overall market shift. In other words, we saw a 'normalisation of terror' following an extended period of continued suicide bombings. The results suggest that investors responded to less transitory global market forces, indicating sustained resilience and long-term market confidence. Future studies directly measuring investor expectations and reactions to man-made disasters, such as terrorism, are warranted. PMID:20735455

  4. Dexamphetamine normalises electrophysiological activity in attention deficit-hyperactivity disorder during the Stroop task.

    PubMed

    Horrobin, S L; McNair, N A; Kirk, I J; Waldie, K E

    2007-10-01

    A case study was conducted to investigate whether dexamphetamine enhances interference control in an adult with attention deficit/hyperactivity disorder. Continuous electroencephalography was recorded both on and off dexamphetamine during performance on a Stroop task. An age-, gender- and IQ-matched control also completed the same task. Event related potentials for the control participant revealed a positive potential to incongruent stimuli between 270 and 440 ms, whereas for the participant with attention deficit/hyperactivity disorder off medication, the reverse polarity was observed in a later time window. Following administration of dexamphetamine, however, the event-related potentials for the incongruent condition closely resembled those in the control, suggesting that dexamphetamine successfully normalises electroencephalographic activity. PMID:18781428

  5. The stories we tell: qualitative research interviews, talking technologies and the 'normalisation' of life with HIV.

    PubMed

    Mazanderani, Fadhila; Paparini, Sara

    2015-04-01

    Since the earliest days of the HIV/AIDS epidemic, talking about the virus has been a key way affected communities have challenged the fear and discrimination directed against them and pressed for urgent medical and political attention. Today, HIV/AIDS is one of the most prolifically and intimately documented of all health conditions, with entrenched infrastructures, practices and technologies--what Vinh-Kim Nguyen has dubbed 'confessional technologies'--aimed at encouraging those affected to share their experiences. Among these technologies, we argue, is the semi-structured interview: the principal methodology used in qualitative social science research focused on patient experiences. Taking the performative nature of the research interview as a talking technology seriously has epistemological implications not merely for how we interpret interview data, but also for how we understand the role of research interviews in the enactment of 'life with HIV'. This paper focuses on one crucial aspect of this enactment: the contemporary 'normalisation' of HIV as 'just another' chronic condition--a process taking place at the level of individual subjectivities, social identities, clinical practices and global health policy, and of which social science research is a vital part. Through an analysis of 76 interviews conducted in London (2009-10), we examine tensions in the experiential narratives of individuals living with HIV in which life with the virus is framed as 'normal', yet where this 'normality' is beset with contradictions and ambiguities. Rather than viewing these as a reflection of resistances to or failures of the enactment of HIV as 'normal', we argue that, insofar as these contradictions are generated by the research interview as a distinct 'talking technology', they emerge as crucial to the normative (re)production of what counts as 'living with HIV' (in the UK) and are an inherent part of the broader performative 'normalisation' of the virus. PMID:25753287

  6. ENEKuS--A Key Model for Managing the Transformation of the Normalisation of the Basque Language in the Workplace

    ERIC Educational Resources Information Center

    Marko, Inazio; Pikabea, Inaki

    2013-01-01

    The aim of this study is to develop a reference model for intervention in the language processes applied to the transformation of language normalisation within organisations of a socio-economic nature. It is based on a case study of an experiment carried out over 10 years within a trade union confederation, and has pursued a strategy of a…

  7. Normalisation of hyperspectral data with respect to illumination and local topography

    NASA Astrophysics Data System (ADS)

    Grumpe, A.; Belkhir, F.; Zirin, V.; Wöhler, C.

    2012-04-01

    Unmixing the apparent reflectance into standard reflectance spectra of so-called endmembers is a common technique in remote sensing of the Moon [Mustard & Pieters 1988]. Recent approaches use distinct features in the reflectance spectrum, such as the depth and position of the minimum of an absorption trough, to estimate elemental abundances of the lunar soil [Wöhler et al. 2010]. It is well known that the apparent reflectance depends on the illumination geometry, and models of the surface reflectance, e.g. the Hapke model [Hapke 1981, 1984, 1986, 2002], were developed. Therefore, a normalisation to a reference geometry is necessary. An important factor governing the illumination geometry is the small-scale topography of the lunar surface. Unfortunately, the lateral resolution of available digital elevation models (DEM) is lower than the lateral resolution of recent spectral observations [Boardman et al. 2011]. Furthermore, the observed radiance is distorted by thermal irradiance [Clark et al. 2011] and might not be pixel-synchronous with the DEM data due to uncertain selenolocation [Boardman et al. 2011]. In this study, we present a general framework to normalise hyperspectral imagery with respect to small-scale topography and variations of illumination geometry. We describe the construction of pixel-synchronous DEMs of very high lateral resolution from single or multiple radiance images using photometric methods [Grumpe & Wöhler 2011]. After correction for thermal radiation, the radiance data are converted to reflectance and normalised to standard geometry (30° incidence angle, 0° emission angle, 30° phase angle) based on the constructed DEMs by applying the Hapke model. We found, however, that this normalisation does not eliminate all topography-related distortions of the spectra, i.e. spectra acquired under standard illumination conditions show different spectral features than spectra of the same lunar surface area acquired under more oblique illumination

  8. Identification of silicon (Si) as an appropriate normaliser for estimating the heavy metals enrichment of an urban lake system.

    PubMed

    Swarnalatha, K; Letha, J; Ayoob, S; Sheela, A M

    2013-11-15

    Urbanisation has a profound influence on our environment, and its burden is often transferred to aquatic systems. The surface sediments of urban lake systems are severely threatened with major contamination on a daily basis. Empirical evidence gleaned from the study of Akkulam Veli, a tropical urban lake in Southern India, indicates the need to evaluate all factors defining the contamination status of lake systems, rather than the conventional procedure that use Al or Fe, and select normalisers to evaluate metal enrichment in contaminated lake systems. A two step correlation analysis was done using Fe, Al, Co, Mn, Ti and Si as normalisers for Cr, Co, Ni, Cu, Zn and Pb. However, Fe, Al, Co, Mn and Ti are found to be unsuitable as normalisers for various reasons, including the redox condition of the lake for Fe, the geological structure of the lake, with its laterite basin that is conducive to high concentrations of Al, the near-detectable range in many stations that can magnify the enrichment for Co, the escalation in EF values for Mn, and the probability of effluent entry from the nearby titanium-based industry for Ti. Si, which is highly refractory, stable, associated with clay minerals, and unaffected by environmental factors such as reduction/oxidation, adsorption/desorption and other diagenic processes, appears to be the most appropriate normaliser in AV lake sediments. The average EF values calculated using Si as a normaliser are Pb (3.88) > Cr (1.77) > Zn (1.71) > Co (1.34) > Cu (1.29) > Ni (0.94). The results of the study show that this alternate method is more accurate at estimating EF values, which in turn can be employed more precisely to evaluate the extent of anthropogenic contamination in urban lake systems with highly contaminated surface sediments. PMID:23792976

  9. Hypertension and aging.

    PubMed

    Buford, Thomas W

    2016-03-01

    Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. However, there are a number of collateral effects, including risks for dementia, physical disability, and falls/fractures which are increasingly garnering attention in the hypertension literature. Several key mechanisms - including inflammation, oxidative stress, and endothelial dysfunction - are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension. PMID:26835847

  10. Cirrhosis and Portal Hypertension

    MedlinePlus

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  11. Evaluation of optimal extracellular vesicle small RNA isolation and qRT-PCR normalisation for serum and urine.

    PubMed

    Crossland, Rachel E; Norden, Jean; Bibby, Louis A; Davis, Joanna; Dickinson, Anne M

    2016-02-01

    MicroRNAs are small regulatory molecules that demonstrate useful biomarker potential. They have been recognised in biofluids, where they are protected from degradation by encapsulation into extracellular vesicles (EVs). A number of commercial products are available for the isolation of EVs and their RNA content; however, extensive protocol comparisons are lacking. Furthermore, robust qRT-PCR assessment of microRNA expression within EVs is problematic, as endogenous controls (ECs) previously used in cellular samples may not be present. This study compares EV isolation and RNA extraction methods (EV precipitation reagents, RNA isolation kits and ultracentrifugation) from serum or urine samples and evaluates suitable ECs for incorporation into qRT-PCR analysis. Results were assessed by electron microscopy, nanoparticle tracking analysis and bioanalyzer concentrations. The stability of 8 ECs was compared for both serum and urine EV RNA and retrospectively validated in independent cohorts (serum n=55, urine n=50). The Life Technologies precipitation reagent gave superior serum EV recovery compared to SBI reagent, as assessed by NTA size distribution, increased RNA concentration, and lower small RNA Ct values. Similarly, the Norgen Biotek Urine Exosome RNA Isolation Kit gave improved results for urine EV isolation compared to ultracentrifugation, when determined by the same parameters. The Qiagen miRNeasy™ RNA isolation kit gave suitable serum EV RNA concentrations compared to other kits, as assessed by Bioanalyzer and small RNA qRT-PCR. Small RNAs HY3 (S.D=1.77, CoV=6.2%) and U6 (S.D=2.14, CoV=8.6%) were selected as optimal ECs for serum EV microRNA expression analysis, while HY3 (S.D=1.67, CoV=6.5%) and RNU48 (S.D=1.85, CoV=5.3%) were identified as suitable for urine studies. In conclusion, this study identifies optimal methods for isolation of serum and urine EV RNA, and suitable ECs for normalisation of qRT-PCR studies. Such reports should aid in the

  12. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT₁R Expression.

    PubMed

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-03-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in N(ω)-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  13. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

    PubMed Central

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-01-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  14. Depression in hypertensive subjects.

    PubMed

    Ramachandran, V; Parikh, G J; Srinivasan, V

    1983-10-01

    168 patients attending hypertension clinic were randomly selected for the study. They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis, Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine and Uric acid level. Detailed psychiatric case history and mental examination was carried out. Beck Rating Scale was used to measure the depression. 25% of hypertensive subjects exhibited depressive features and their mean score in Beck Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic. No significant difference in the incidence of depression with the duration of medication was observed.The hypertension was classified into mild, moderate and severe depending on the diastolic pressure. Depression was more frequent in severe hypertensives but not to the statistically significant level.Further hypertensives were classified into:1. Hypertension without organ involvement2. Hypertension with LVH only3. Hypertension with additional organ involvement4. Malignant hypertensionDepression was significantly more frequent in hypertensives with complications and also hypertensives in whom the B.P. remained uncontrolled. As all the patients were on the same drug, the drug effect is common to all; hence, the higher incidence of depression in hypertensives with complications is due to the limitation and distress caused by the illness. PMID:21847301

  15. Renal denervation for severe hypertension in a small child with Turner syndrome: miniaturisation of the procedure and results.

    PubMed

    Bonanni, Alice; Pasetti, Francesco; Ghiggeri, Gian Marco; Gandolfo, Carlo

    2015-01-01

    Sympathetic nervous system hyperactivity plays a role in development and progression of hypertension. While renal denervation employing radiofrequency devices has been used therapeutically in treating severe hypertension with alternate results in adults, few data are available regarding children. We treated a 6-year-old girl affected by Turner syndrome presenting severe hypertension and an episode of stroke, in spite of treatment with four antihypertensive drugs, with sympathetic ablation. The Simplicity device (Medtronic, Minneapolis, USA) was adapted to the smaller vessels, allowing a tailored approach. After 3 and 6 months of treatment, and β-blocker discontinuation, blood pressure values were set between the 90th and 95th centiles for sex and age, and normalised at 12 months. We confirm that renal denervation can be used to treat severe hypertension in children; miniaturisation of catheter and tailoring the procedure for small vessels allowed a safe approach. Progressive improvement of blood pressure had a satisfactory clinical impact. PMID:25759273

  16. DC-Electrical Resistivity Imaging for embankment dike investigation: A 3D extended normalisation approach

    NASA Astrophysics Data System (ADS)

    Fargier, Yannick; Lopes, Sérgio Palma; Fauchard, Cyrille; François, Daniel; Côte, Philippe

    2014-04-01

    Levee, dike and earth embankment dam structures are difficult to assess because of their length and complexity. Managers often include geophysical investigations in the overall dike condition assessment and the DC-Electrical Resistivity Imaging (ERI) method is particularly applicable owing to its cost-effectiveness and its potential sensitivity to internal erosion. However, due to the truly 3D nature of embankment dikes, implementing inline longitudinal tomographies along with conventional 2D inversion is likely to yield image artefacts. 3D effects from external causes (geometry, water reservoir) can be predicted and therefore we present a new approach based on redefining the normalisation principle to derive apparent resistivities from the measured data. The aim is to provide a set of pre-processed apparent resistivities that are not contaminated by external 3D effects and that yield more reliable results when processed within a 2D conventional inversion scheme. The presented approach is successfully applied to synthetic and real data sets, proving superior to the conventional 2D approach, although data acquisition approach is the same thus keeping the same cost-effectiveness.

  17. New developments in the pathogenesis of obesity-induced hypertension.

    PubMed

    Kotsis, Vasilios; Nilsson, Peter; Grassi, Guido; Mancia, Giuseppe; Redon, Josep; Luft, Frank; Schmieder, Roland; Engeli, Stefan; Stabouli, Stella; Antza, Christina; Pall, Denes; Schlaich, Markus; Jordan, Jens

    2015-08-01

    Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity. PMID:26103132

  18. Purinergic dysregulation in pulmonary hypertension.

    PubMed

    Visovatti, Scott H; Hyman, Matthew C; Goonewardena, Sascha N; Anyanwu, Anuli C; Kanthi, Yogendra; Robichaud, Patrick; Wang, Jintao; Petrovic-Djergovic, Danica; Rattan, Rahul; Burant, Charles F; Pinsky, David J

    2016-07-01

    Despite the fact that nucleotides and adenosine help regulate vascular tone through purinergic signaling pathways, little is known regarding their contributions to the pathobiology of pulmonary arterial hypertension, a condition characterized by elevated pulmonary vascular resistance and remodeling. Even less is known about the potential role that alterations in CD39 (ENTPD1), the ectonucleotidase responsible for the conversion of the nucleotides ATP and ADP to AMP, may play in pulmonary arterial hypertension. In this study we identified decreased CD39 expression on the pulmonary endothelium of patients with idiopathic pulmonary arterial hypertension. We next determined the effects of CD39 gene deletion in mice exposed to normoxia or normobaric hypoxia (10% oxygen). Compared with controls, hypoxic CD39(-/-) mice were found to have a markedly elevated ATP-to-adenosine ratio, higher pulmonary arterial pressures, more right ventricular hypertrophy, more arterial medial hypertrophy, and a pro-thrombotic phenotype. In addition, hypoxic CD39(-/-) mice exhibited a marked increase in lung P2X1 receptors. Systemic reconstitution of ATPase and ADPase enzymatic activities through continuous administration of apyrase decreased pulmonary arterial pressures in hypoxic CD39(-/-) mice to levels found in hypoxic CD39(+/+) controls. Treatment with NF279, a potent and selective P2X1 receptor antagonist, lowered pulmonary arterial pressures even further. Our study is the first to implicate decreased CD39 and resultant alterations in circulating purinergic signaling ligands and cognate receptors in the pathobiology of pulmonary arterial hypertension. Reconstitution and receptor blocking experiments suggest that phosphohydrolysis of purinergic nucleotide tri- and diphosphates, or blocking of the P2X1 receptor could serve as treatment for pulmonary arterial hypertension. PMID:27208163

  19. Comparative Normalisation Analysis (CNA) of the Imbrium region using Near-Infrared data from the SIR-2 instrument

    NASA Astrophysics Data System (ADS)

    Bugiolacchi, R.; Mall, U.

    2013-09-01

    A Comparative Normalisation Analysis (CNA) method takes advantage of the two main strengths of the SIR-2 instrument: its high spectral resolution and, crucially, the uniformity and comparability between the spectral samples obtained during its 100 km altitude mission phase as part of the Chandrayyan-1 payload. The analysed data is classified according to spectral absorption characteristics and binned within ten chosen classes. Geographical distribution maps are produced and thence discussed in a geological context.

  20. Selective normalisation of regional brain bis(monoacylglycero)phosphate in the mucopolysaccharidosis 1 (Hurler) mouse.

    PubMed

    Saville, Jennifer T; Lehmann, Rebecca J; Derrick-Roberts, Ainslie L K; Fuller, Maria

    2016-03-01

    Bis(monoacylglycero)phosphate (BMP) is a glycerophospholipid highly enriched in the lysosomal network and elevated in lysosomal diseases. To correct this elevation, BMP synthesis was manipulated by dietary fatty acid supplementation and the impact on subregional brain BMP and pathology assessed in the mouse model of mucopolysaccharidosis 1 (Hurler syndrome (HS)). There was widespread elevation of BMP in HS mice across all six sub-regions - brain stem, cortex, cerebellum, hippocampus, olfactory bulb and the sub-cortex - with 22:6/22:6 the most abundant species. Linoleic acid normalised total BMP in all regions except the cortex and cerebellum, although there were differences in fatty acid species; the major finding a decrease in 22:6- and a concomitant increase in 22:5-containing species. A battery of behaviour assessments showed that in the water cross maze both HS and wild type mice performed less well on the linoleic acid diet, and that both HS and wild type mice on the linoleic acid diet performed similarly and better in the exploratory open field test. This may be a consequence of differential subregional BMP composition in the brain. The effects of high fat and docosahexaenoic/eicosapentaenoic acid enriched diets were generally unremarkable. Although major pathologies were not completely abrogated, much of the neurobehavioural testing was confounded by skeletal pathology that did not resolve. This is the first detailed characterisation of subregional brain BMP species informing on the ability to manipulate this phospholipid in the brain, and as such, may hold promise as an adjunct therapy not only for HS but also for other lysosomal diseases. PMID:26710715

  1. The centre of rotation of the shoulder complex and the effect of normalisation.

    PubMed

    Amabile, Celia; Bull, Anthony M J; Kedgley, Angela E

    2016-06-14

    Shoulder motions consist of a composite movement of three joints and one pseudo-joint, which together dictate the humerothoracic motion. The purpose of this work was to quantify the location of the centre of rotation (CoR) of the shoulder complex as a whole. Dynamic motion of 12 participants was recorded using optical motion tracking during coronal, scapular and sagittal plane elevation. The instantaneous CoR was found for each angle of elevation using helical axes projected onto the three planes of motion. The location of an average CoR for each plane was evaluated using digitised and anthropometric measures for normalisation. When conducting motion in the coronal, scapular, and sagittal planes, respectively, the coefficients for locating the CoRs of the shoulder complex are -61%, -61%, and -65% of the anterior-posterior dimension - the vector between the midpoint of the incisura jugularis and the xiphoid process and the midpoint of the seventh cervical vertebra and the eighth thoracic vertebra; 0%, -1%, and -2% of the superior-inferior dimension - the vector between the midpoint of the acromioclavicular joints and the midpoint of the anterior superior iliac spines; and 57%, 57%, and 78% of the medial-lateral dimension -0.129 times the height of the participant. Knowing the location of the CoR of the shoulder complex as a whole enables improved participant positioning for evaluation and rehabilitation activities that involve movement of the hand with a fixed radius, such as those that employ isokinetic dynamometers. PMID:27048984

  2. Valproate Induced Hypertensive Urgency

    PubMed Central

    Sivananthan, Mauran

    2016-01-01

    Valproate is a medication used in the treatment of seizures, bipolar disorder, migraines, and behavioral problems. Here we present a case of an 8-year-old boy who presented with hypertensive urgency after initiation of valproate. Primary treatment of his hypertension was ineffective. Blood pressure stabilization was achieved following discontinuation of valproate. Clinicians should be aware of the risk of developing hypertensive urgency with administration of valproate. PMID:27403366

  3. Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension

    PubMed Central

    Wang, La-mei; Tang, Na; Zhong, Hua; Liu, Yong-min; Li, Zhen; Feng, Qian; He, Fang

    2016-01-01

    The proliferation of vascular smooth muscle cells (VSMCs), remodeling of the vasculature, and the renin-angiotensin system (RAS) play important roles in the development of essential hypertension (EH), which is defined as high blood pressure (BP) in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR) is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs) and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%), total vessel wall cross-sectional area to the total area (WA%) of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA%) were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP), renin, and angiotensin II (Ang II) were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH. PMID:27391973

  4. Pediatric endocrine hypertension

    PubMed Central

    Bhavani, Nisha

    2011-01-01

    Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

  5. Hypertensive emergencies in pregnancy.

    PubMed

    Vadhera, Rakesh B; Simon, Michelle

    2014-12-01

    Hypertensive disorders of pregnancy complicate 7% to 10% of pregnancies and are among the major causes of maternal and perinatal morbidity and mortality. Recently American College of Obstetricians and Gynecologists Taskforce on Hypertension during Pregnancy modified the diagnosis and management of hypertension in pregnancy, recommending prompt diagnosis, admission, close monitoring, and treatment. They strive to decrease maternal mortality and systemic complications. Labetalol, hydralazine, or nifedipine are considered first-line treatment, and either can be used to stabilize the patient with similar outcomes. Definite treatment is delivery of the fetus and should be considered based on the etiology of the hypertensive crisis and gestational age. PMID:25314092

  6. How Is Pulmonary Hypertension Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) ... To Look for the Underlying Cause of Pulmonary Hypertension PH has many causes, so many tests may ...

  7. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    MedlinePlus

    ... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

  8. Hypoxia Inducible Factors and Hypertension: Lessons from Sleep Apnea Syndrome

    PubMed Central

    Nanduri, Jayasri; Peng, Ying-Jie; Yuan, Guoxiang; Kumar, Ganesh K.; Prabhakar, Nanduri R.

    2015-01-01

    Systemic hypertension is one of the most prevalent cardiovascular diseases. Sleep disordered breathing (SDB) with recurrent apnea is a major risk factor for developing essential hypertension. Chronic intermittent hypoxia (CIH) is a hallmark manifestation of recurrent apnea. Rodent models patterned after the O2 profiles seen with SDB patients showed that CIH is the major stimulus for causing systemic hypertension. This article reviews the physiological and molecular basis of CIH-induced hypertension. Physiological studies have identified that augmented carotid body chemosensory reflex and the resulting increase in sympathetic nerve activity is a major contributor to CIH-induced hypertension. Analysis of molecular mechanisms revealed that CIH activates hypoxia-inducible factor (HIF)-1 and suppresses HIF-2- mediated transcription. Dysregulation of HIF-1- and HIF-2- mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme gene expression resulting in increased reactive species (ROS) generation in the chemosensory reflex which is central for developing hypertension. PMID:25772710

  9. The effect of moderate-intensity exercise on the expression of HO-1 mRNA and activity of HO in cardiac and vascular smooth muscle of spontaneously hypertensive rats.

    PubMed

    Ren, Cailing; Qi, Jie; Li, Wanwei; Zhang, Jun

    2016-04-01

    The objective of this study was to observe the effects of moderate-intensity training on the activity of heme oxygenase (HO) and expression of HO-1 mRNA in the aorta and the cardiac muscle of spontaneously hypertensive rats (SHRs). After 9 weeks of swimming exercise, the activity of HO and expression of HO-1 mRNA in the SHRs were measured. The resting blood pressure in the exercise group was increased by 1.7% (P > 0.05), whereas it was significantly elevated by 10.3% (P < 0.01) in the SHR rats. Compared with animals in the control and sedentary groups, the expression level of HO-1 mRNA of aorta and cardiac muscle in the exercise group was significantly enhanced (P < 0.01). The HO activity and the content of plasma carbon monoxide (CO) in the sedentary group were dramatically decreased (P < 0.05 and P < 0.01, respectively) compared with the control group. HO activity and content of plasma CO in the exercise group were significantly higher compared with those in the sedentary group (P < 0.05 and P < 0.01, respectively). The HO/CO metabolic pathway might be involved in the regulation of blood pressure of the SHR models. PMID:26928589

  10. Hypertension in the military patient.

    PubMed

    Hunter, Alys; Holdsworth, D A; D'Arcy, J; Bailey, K; Casadei, B

    2015-09-01

    Hypertension and hypertension-related diseases are a leading cause of morbidity and mortality worldwide. A diagnosis of hypertension can have serious occupational implications for military personnel. This article examines the diagnosis and management of hypertension in military personnel, in the context of current international standards. We consider the consequences of hypertension in the military environment and potential military-specific issues relating to hypertension. PMID:26253125

  11. Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes

    PubMed Central

    Teo, Karen SL; Dundon, Benjamin K; Molaee, Payman; Williams, Kerry F; Carbone, Angelo; Brown, Michael A; Worthley, Matthew I; Disney, Patrick J; Sanders, Prashanthan; Worthley, Stephen G

    2008-01-01

    normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures. PMID:19040763

  12. Epigenetic Modifications in Essential Hypertension

    PubMed Central

    Wise, Ingrid A.; Charchar, Fadi J.

    2016-01-01

    Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. PMID:27023534

  13. Noncirrhotic Portal Hypertension

    PubMed Central

    Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

  14. What Is Pulmonary Hypertension?

    MedlinePlus

    ... Pressure Tools & Resources Stroke More What is Pulmonary Hypertension? Updated:Aug 12,2014 Is pulmonary hypertension different ... content was last reviewed on 08/04/2014. High Blood Pressure • Home • About High Blood Pressure (HBP) Introduction What ...

  15. Hypertension and cognitive function.

    PubMed

    Paglieri, Cristina; Bisbocci, Daniela; Caserta, Mimma; Rabbia, Franco; Bertello, Chiara; Canadè, Antonella; Veglio, Franco

    2008-11-01

    Arterial hypertension, cerebrovascular disease, and dementia are related pathologies. This paper has reviewed comparatively the incidence of arterial hypertension and adult-onset dementia disorders. Hypertension is associated with cerebrovascular disease, which is in turn associated with dementia. It is the most important modifiable risk factor for stroke, which is a recognized cause of vascular dementia. In terms of pathophysiology of hypertensive brain damage, several hypotheses were developed, such as that vascular alterations induced by hypertension can induce lacunar or cortical infarcts and leucoaraiosis, that hypertension is responsible for cerebrovascular disease and acts into the contest of a pre-existing subclinic Alzheimer's disease (AD), that hypertension determines neurobiologic alterations (such as beta-amyloid accumulation) resulting in neuropathologic damage, and that aging and cerebrovascular risk factors act together to cause cerebral capillary degeneration, mitochondrial disruption, reduced glucose oxidation, and reduced ATP synthesis. The consequence of these alterations are neuronal death and dementia. Macroscopic results of these mechanisms are the so-called white matter lesions (WML), the significance of which is analyzed. Increasing clinical evidence suggests a close relationship between the reduction of elevated blood pressure and countering of both vascular dementia and AD. Antihypertensive treatment probably influences cognitive performances and prevents cognitive function alterations and the development of dementia. It is therefore important to evaluate as soon as possible cognitive functions of hypertensive patients. PMID:19021021

  16. Hypertension in the elderly

    PubMed Central

    Lionakis, Nikolaos; Mendrinos, Dimitrios; Sanidas, Elias; Favatas, Georgios; Georgopoulou, Maria

    2012-01-01

    The elderly are the most rapidly growing population group in the world. Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. The risk of coronary artery disease, stroke, congestive heart disease, chronic kidney insufficiency and dementia is also increased in this subgroup of hypertensives. Hypertension in the elderly patients represents a management dilemma to cardiovascular specialists and other practioners. During the last years and before the findings of the Systolic Hypertension in Europe Trial were published, the general medical opinion considered not to decrease blood pressure values similarly to other younger patients, in order to avoid possible ischemic events and poor oxygenation of the organs (brain, heart, kidney). The aim of this review article is to highlight the importance of treating hypertension in aged population in order to improve their quality of life and lower the incidence of the cardiovascular complications. PMID:22655162

  17. Cervical Spondylosis and Hypertension

    PubMed Central

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion. Stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo and hypertension. In addition, chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary hypertension. Early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis. PMID:25761188

  18. Emotions in vowel segments of continuous speech: analysis of the glottal flow using the normalised amplitude quotient.

    PubMed

    Airas, Matti; Alku, Paavo

    2006-01-01

    Emotions in short vowel segments of continuous speech were analysed using inverse filtering and a recently developed glottal flow parameter, the normalised amplitude quotient (NAQ). Simulated emotion portrayals were produced by 9 professional stage actors. Separated /a:/ vowel segments were inverse filtered and parameterized using NAQ. Statistical analyses showed significant differences among most of the emotions studied. Results also demonstrated clear gender differences. Inverse filtering, together with NAQ, was shown to be a promising method for the analysis of emotional content in continuous speech. PMID:16514274

  19. Hypertension alters phosphorylation of VASP in brain endothelial cells.

    PubMed

    Arlier, Zulfikar; Basar, Murat; Kocamaz, Erdogan; Kiraz, Kemal; Tanriover, Gamze; Kocer, Gunnur; Arlier, Sefa; Giray, Semih; Nasırcılar, Seher; Gunduz, Filiz; Senturk, Umit K; Demir, Necdet

    2015-04-01

    Hypertension impairs cerebral vascular function. Vasodilator-stimulated phosphoprotein (VASP) mediates active reorganization of the cytoskeleton via membrane ruffling, aggregation and tethering of actin filaments. VASP regulation of endothelial barrier function has been demonstrated by studies using VASP(-/-) animals under conditions associated with tissue hypoxia. We hypothesize that hypertension regulates VASP expression and/or phosphorylation in endothelial cells, thereby contributing to dysfunction in the cerebral vasculature. Because exercise has direct and indirect salutary effects on vascular systems that have been damaged by hypertension, we also investigated the effect of exercise on maintenance of VASP expression and/or phosphorylation. We used immunohistochemistry, Western blotting and immunocytochemistry to examine the effect of hypertension on VASP expression and phosphorylation in brain endothelial cells in normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive (SH) rats under normal and exercise conditions. In addition, we analyzed VASP regulation in normoxia- and hypoxia-induced endothelial cells. Brain endothelial cells exhibited significantly lower VASP immunoreactivity and phosphorylation at the Ser157 residue in SHR versus WKY rats. Exercise reversed hypertension-induced alterations in VASP phosphorylation. Western blotting and immunocytochemistry indicated reduction in VASP phosphorylation in hypoxic versus normoxic endothelial cells. These results suggest that diminished VASP expression and/or Ser157 phosphorylation mediates endothelial changes associated with hypertension and exercise may normalize these changes, at least in part, by restoring VASP phosphorylation. PMID:24894047

  20. Resistant hypertension - an update.

    PubMed

    Pasha, K; Towhiduzzaman, M; Manwar, A; Jahan, M U

    2015-04-01

    Patients with hypertension are increasing in Bangladesh. Among these patients a growing number of patients are having resistant hypertension faced by both primary care physicians and specialists. There is no data regarding prevalence of resistant hypertension in Bangladesh, but clinical trials abroad suggests that it is not rare, involving perhaps 20% to 30% of study participants. Cardiovascular risk is undoubtedly increased in such patients and the condition is often complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multi drug regimens. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; presence of multiple disease processes and their associated medical therapies, which confound interpretation of study results. Therefore we should concentrate on expanding our knowledge of the causes of resistant hypertension which will allow for more effective prevention and/or treatment which is essential to improve long-term clinical management of this condition. PMID:26007281

  1. Presence of mutation m.14484T>C in a Chinese family with maternally inherited essential hypertension but no expression of LHON.

    PubMed

    Guo, Hao; Zhuang, Xin-Ying; Zhang, A-Mei; Zhang, Wen; Yuan, Yong; Guo, Li; Yu, Dandan; Liu, Juan; Yang, Da-Kuan; Yao, Yong-Gang

    2012-10-01

    Essential hypertension (EH, MIM 145500) is the most common cardiovascular disease and affects one-quarter of the world's adult population. Families with EH in a mode of maternal transmission have been occasionally observed in clinical settings and suggested an involvement of mitochondrial DNA (mtDNA) mutation. We aimed to characterize the role of mtDNA mutation in EH. We reported a large Han Chinese family with a maternally inherited EH and an extraordinarily high percentage of sudden death mainly in affected females. Analysis of the entire mtDNA genome of the proband identified a homoplasmic primary mutation m.14484T>C for Leber's hereditary optic neuropathy (LHON), along with several variants indicating haplogroup F1 status. Intriguingly, no maternal member in this family had LHON though they all harbored m.14484T>C. The arterial stiffness of the members carrying mutation m.14484T>C was significantly increased than that of non-maternal members without this mutation. No environmental factor (including age, sex, smoking, diabetes, hyperlipidemia) was correlated with the decreased aortic elastic properties observed in affected members. Mitochondrial respiration rate and membrane potential (ΔΨ(m)) were significantly reduced in lymphoblastoid cell lines established from affected members carrying m.14484T>C when compared to control cell lines (P<0.05). There was an elevation of reactive oxygen species and a compensatory increase of mitochondrial mass in mutant cell lines. Our results suggest that m.14484T>C causes EH under certain circumstance. This study provides a paradigm for diverse phenotypes of the primary LHON mutation and suggests for the necessity of routine cardiac evaluation in patients with the primary LHON mutation. PMID:22749828

  2. Update in Hypertension Therapy.

    PubMed

    Mankin, Leonard A

    2016-07-01

    Hypertension is the leading cause of early mortality in the world, and reduction of blood pressure can help to reduce that burden. There is an enormous and ever-expanding body of literature on hypertension, with a 2016 Medline search for hypertension retrieving more than 113,000 publications. Recent guidelines from major societies have been published, and often present conflicting recommendations based on the same data. Using a question-and-answer format, this article reviews some of the recent developments and opinions on management of blood pressure and provides practical suggestions for management in the clinical arena. PMID:27235610

  3. Perioperative hypertension management

    PubMed Central

    Varon, Joseph; Marik, Paul E

    2008-01-01

    Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

  4. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases. PMID:26587450

  5. Hypertension in the athlete.

    PubMed

    Sachtleben, Thomas; Fields, Karl B

    2003-04-01

    Athletes with hypertension are frequently encountered in clinical settings and during preparticipation examinations. This common condition merits special attention in athletes, as they have particular physiologic and sport-specific demands. Awareness of the pressor response to both isometric and isotonic exercise is valuable in managing hypertensive athletes. Recommendations regarding physical activity in hypertensive patients and clearance for sports participation among competitive athletes are reviewed. Nonpharmacologic measures and the use of customary antihypertensives in athletes is essential. However, knowledge of side-effect profiles and possible negative effects on exercise tolerance guide appropriate medication choices. PMID:12831663

  6. Hypothalamic signaling mechanisms in hypertension.

    PubMed

    Carmichael, Casey Y; Wainford, Richard D

    2015-05-01

    The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension. PMID:25860531

  7. A Novel Channelopathy in Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Eric D.; Eyries, Mélanie; Sampson, Kevin S.; Soubrier, Florent; Germain, Marine; Trégouët, David-Alexandre; Borczuk, Alain; Rosenzweig, Erika Berman; Girerd, Barbara; Montani, David; Humbert, Marc; Loyd, James E.; Kass, Robert S.; Chung, Wendy K.

    2013-01-01

    BACKGROUND Pulmonary arterial hypertension is a devastating disease with high mortality. Familial cases of pulmonary arterial hypertension are usually characterized by autosomal dominant transmission with reduced penetrance, and some familial cases have unknown genetic causes. METHODS We studied a family in which multiple members had pulmonary arterial hypertension without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic pulmonary arterial hypertension were screened for the mutations in the gene that was identified on whole-exome sequencing. All variants were expressed in COS-7 cells, and channel function was studied by means of patch-clamp analysis. RESULTS We identified a novel heterozygous missense variant c.608 G→A (G203D) in KCNK3 (the gene encoding potassium channel subfamily K, member 3) as a disease-causing candidate gene in the family. Five additional heterozygous missense variants in KCNK3 were independently identified in 92 unrelated patients with familial pulmonary arterial hypertension and 230 patients with idiopathic pulmonary arterial hypertension. We used in silico bioinformatic tools to predict that all six novel variants would be damaging. Electrophysiological studies of the channel indicated that all these missense mutations resulted in loss of function, and the reduction in the potassium-channel current was remedied by the application of the phospholipase inhibitor ONO-RS-082. CONCLUSIONS Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension. Mutations in this gene produced reduced potassium-channel current, which was successfully remedied by pharmacologic manipulation. (Funded by the National Institutes of Health.) PMID:23883380

  8. MicroRNAs in Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Guofei; Chen, Tianji

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  9. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    PubMed Central

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. PMID:24533144

  10. MicroRNAs in pulmonary arterial hypertension.

    PubMed

    Zhou, Guofei; Chen, Tianji; Raj, J Usha

    2015-02-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  11. Changes in Caspase-3, B Cell Leukemia/Lymphoma-2, Interleukin-6, Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor Gene Expression after Human Umbilical Cord Blood Derived Mesenchymal Stem Cells Transfusion in Pulmonary Hypertension Rat Models

    PubMed Central

    Kim, Kwan Chang; Lee, Jae Chul; Lee, Hyeryon; Cho, Min-Sun; Choi, Soo Jin

    2016-01-01

    Background and Objectives Failure of vascular smooth muscle apoptosis and inflammatory response in pulmonary arterial hypertension (PAH) is a current research focus. The goals of this study were to determine changes in select gene expressions in monocrotaline (MCT)-induced PAH rat models after human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) transfusion. Materials and Methods The rats were separated into 3 groups i.e., control group (C group), M group (MCT 60 mg/kg), and U group (hUCB-MSCs transfusion) a week after MCT injection. Results TUNEL assay showed that the U group had significantly lowered positive apoptotic cells in the lung tissues, as compared with the M group. mRNA of caspase-3, B cell leukemia/lymphoma (Bcl)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in the lung tissues were greatly reduced at week 4 in the U group. Immunohistochemical staining of the lung tissues also demonstrated a similar pattern, with the exception of IL-6. The protein expression of caspase-3, Bcl-2 VEGF, IL-6, TNF-α and brain natriuretic peptide in the heart tissues were significantly lower in the U group, as compared with the M group at week 2. Furthermore, the protein expression of VEGF, IL-6 and BNP in the heart tissues were significantly lower in the U group at week 4. Collagen content in the heart tissues was significantly lower in the U group, as compared with M group at weeks 2 and 4, respectively. Conclusion hUCB-MSCs could prevent inflammation, apoptosis and remodeling in MCT-induced PAH rat models. PMID:26798389

  12. Secondary hypertension in adults

    PubMed Central

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-01-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. PMID:27211205

  13. Hypertensive heart disease

    MedlinePlus

    ... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  14. Hypertension (High Blood Pressure)

    MedlinePlus

    ... pressure to live. Without it, blood can't flow through our bodies and carry oxygen to our vital organs. But when blood pressure gets too high — a condition called hypertension — it can lead to ...

  15. High Blood Pressure (Hypertension)

    MedlinePlus

    ... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has high ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

  16. Hypertension (High Blood Pressure)

    MedlinePlus

    ... blood pressure with the development of a practical method to measure it. Physicians began to note associations between hypertension and risk of heart failure, stroke, and kidney failure. Although scientists had yet to prove that lowering blood pressure ...

  17. Effect of exercise on hyperactivity, impulsivity and dopamine D2 receptor expression in the substantia nigra and striatum of spontaneous hypertensive rats

    PubMed Central

    Cho, Han Sam; Baek, Dae Jung; Baek, Seung Soo

    2014-01-01

    [Purpose] Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurobehavioral disorder that is characterized by hyperactivity, inattention, and impulsivity. It is commonly believed that the symptoms of ADHD are closely associated with hypo-function of the dopamine system. Dopamine D2 receptor activation decreases the excitability of dopamine neurons, as well as the release of dopamine. Physical exercise is known to improve structural and functional impairments in neuropsychiatric disorders. We investigated the therapeutic effect of exercise on ADHD. [Methods] Open field task and elevated-plus maze task were used in the evaluation of hyperactivity and impulsivity, respectively. Dopamine D2 receptor expression in the substantia nigra and striatum were evaluated by western blotting. [Results] The present results indicated that ADHD rats showed hyperactivity and impulsivity. Dopamine D2 receptor expression in the substantia nigra and striatum were increased in ADHD rats. Exercise alleviated hyperactivity and impulsivity in ADHD rats. Furthermore, dopamine D2 receptor expression in ADHD rats was also decreased by exercise. [Conclusion] We thus showed that exercise effectively alleviates ADHD-induced symptoms through enhancing dopamine D2 expression in the brain. PMID:25671205

  18. Cost of hypertension treatment.

    PubMed

    Odell, T W; Gregory, M C

    1995-12-01

    A retrospective analysis was conducted of the cost of hypertension care at one internal medicine clinic, looking at the cost of office visits, laboratory tests, and medications. Cost of hypertension care was $947 the first year of treatment, $575 the second year, and $420 per year thereafter. Drug costs were the major determinant of cost of care, comprising 80% of the total cost of treatment after the first year of therapy. PMID:8770721

  19. Hypertensive emergencies of pregnancy.

    PubMed

    Alexander, James M; Wilson, Karen L

    2013-03-01

    Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent. PMID:23466139

  20. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  1. Resistant Hypertension and Chronotherapy

    PubMed Central

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-01-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing’s syndrome, thyroid diseases, aortic coarctation. For diagnosing patient’s history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of “non-dipper” hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  2. Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children

    PubMed Central

    Övünç Hacıhamdioğlu, Duygu; Zeybek, Cengiz; Gök, Faysal; Pekel, Aysel; Muşabak, Uğur

    2015-01-01

    Objective: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. Methods: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. Results: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05). Conclusion: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension. PMID:26831550

  3. Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

    PubMed

    Itani, Hana A; Dikalova, Anna E; McMaster, William G; Nazarewicz, Rafal R; Bikineyeva, Alfiya T; Harrison, David G; Dikalov, Sergey I

    2016-06-01

    Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension. PMID:27067720

  4. [Hypertensive crisis in kidney patients].

    PubMed

    Scrivano, Jacopo; Giuliani, Anna; Pettorini, Laura; Punzo, Giorgio; Mene', Paolo; Pirozzi, Nicola

    2011-01-01

    The classification and management of hypertensive crisis have been recently reviewed in the context of both European and American guidelines. The key points for proper blood pressure control in severe arterial hypertension are: 1 - Distinction between urgent intervention and emergencies 2 - Choice of the best drug(s) 3 - Choice of the correct route of administration. In patients with renal disease, beside the common causes of hypertension/ hypertensive crises, kidney-specific causes should be taken into account such as renal parenchymal hypertension, renovascular hypertension, sclerodermic crises, and preeclampsia. PMID:22028263

  5. The A Allele of the rs1990760 Polymorphism in the IFIH1 Gene Is Associated with Protection for Arterial Hypertension in Type 1 Diabetic Patients and with Expression of This Gene in Human Mononuclear Cells

    PubMed Central

    Bouças, Ana P.; Brondani, Letícia A.; Souza, Bianca M.; Lemos, Natália E.; de Oliveira, Fernanda S.; Canani, Luis H.; Crispim, Daisy

    2013-01-01

    Background The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associated with T1DM. Methods Frequencies of the rs1990760 polymorphism were analyzed in 527 T1DM patients and in 517 healthy subjects. IFIH1 gene expressions according to genotypes were measured in a sub-sample of 26 T1DM patients by quantitative real-time PCR. Results Our data show the association of the A allele with risk to T1DM under a dominant model of inheritance [odds ratio (OR) = 1.421, P = 0.037], adjusting for ethnicity. The meta-analysis revealed significant association between the rs199760A allele and risk for T1DM for all analyzed inheritance models. Surprisingly, T1DM patients carrying the A allele showed lower levels of systolic (P = 0.001) and diastolic (P = 1×10−10) blood pressures as compared to G/G carriers. Furthermore, the A/A genotype seems to be associated with protection to arterial hypertension (AH) after adjustment for covariates (OR = 0.339, P = 0.019). IFIH1 gene expression in mononuclear cells from 26 T1DM patients did not differ among genotypes (P = 0.274). Nevertheless, IFIH1 gene expression was increased in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [6.7 (1.7–2.0) vs. 1.8 (1.3–7.1) arbitrary units; P = 0.036]. The association with blood pressures and AH was not observed in patients with type 2 diabetes mellitus. Conclusions Our results indicate that the rs1990760 polymorphism is associated with T1DM. Interestingly, the rs1990760 A allele seems to be associated with

  6. From theory to 'measurement' in complex interventions: Methodological lessons from the development of an e-health normalisation instrument

    PubMed Central

    2012-01-01

    Background Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field. Methods A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals. Results The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation ‘processes’ were significantly related to staff members’ perceptions of whether or not e-health had become ‘routine’. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts. Conclusions To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3

  7. Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents

    PubMed Central

    Chuang, Jie-Yu; J Whitaker, Kirstie; Murray, Graham K; Elliott, Rebecca; Hagan, Cindy C; Graham, Julia ME; Ooi, Cinly; Tait, Roger; Holt, Rosemary J; van Nieuwenhuizen, Adrienne O; Reynolds, Shirley; Wilkinson, Paul O; Bullmore, Edward T; Lennox, Belinda R; Sahakian, Barbara J; Goodyer, Ian; Suckling, John

    2016-01-01

    Background Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. Methods Eighty-two Depressed and 24 healthy female adolescents, aged 12–17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. Results At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35–13.27) were related at trend-level to activation changes in orbitofrontal cortex. Limitations In the follow-up section, a limited number of post-CBT patients were recruited. Conclusions To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration. PMID:26406969

  8. Pregnancy with Portal Hypertension

    PubMed Central

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  9. DNA Damage and Pulmonary Hypertension

    PubMed Central

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  10. DNA Damage and Pulmonary Hypertension.

    PubMed

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  11. Stress and hypertension.

    PubMed Central

    Mustacchi, P.

    1990-01-01

    In susceptible persons emotional stress results in immediate sympathetic stimulation, with a vasomotor response that results in a high-output state and elevated blood pressure; the vasopressor response seems to be transient. There seems to be no longitudinal epidemiologic validation of the attractive hypothesis that transiently elevated blood pressures are the prelude to fixed hypertension, however. The acquisition of hypertension by populations abandoning their traditional mode of living has been attributed to the sociocultural stress inherent in westernization, but these studies usually have not taken into account concomitants of this type of acculturation, such as dietary changes and increased body weight. The inverse relationship of blood pressure levels to education could explain the development of hypertension when aspiration to upward mobility is thwarted. The severity of perceived occupational stress relates inversely to blood pressure, suggesting that familiarity with a job renders the demands made by the work environment more predictable and less threatening in terms of vasopressor response. PMID:2219875

  12. Hypertension and cerebrovascular damage.

    PubMed

    Veglio, Franco; Paglieri, Cristina; Rabbia, Franco; Bisbocci, Daniela; Bergui, Mauro; Cerrato, Paolo

    2009-08-01

    Hypertension is the most important modifiable factor for cerebrovascular disease. Stroke and dementia are growing health problems that have considerable social and economical consequences. Hypertension causes brain lesions by several mechanisms predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as well as to intracerebral haemorrhages. These parenchymal damages determine evident or silent neurological alterations that often precede the onset of cognitive decline. It is important to recognize cerebrovascular disease and, above all, to correlate typical lesions to hypertension. Antihypertensive therapy has shown clinical benefits in primary and secondary prevention of stroke. These drugs represent important instruments against cerebrovascular disease but their effects on cognition are still matter of debate. Cerebral parenchymal and functional damages have to be considered together to make medical intervention more incisive. PMID:19100549

  13. Chronic thromboembolic pulmonary hypertension.

    PubMed

    O'Connell, Caroline; Montani, David; Savale, Laurent; Sitbon, Olivier; Parent, Florence; Seferian, Andrei; Bulifon, Sophie; Fadel, Elie; Mercier, Olaf; Mussot, Sacha; Fabre, Dominique; Dartevelle, Philippe; Humbert, Marc; Simonneau, Gérald; Jaïs, Xavier

    2015-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) characterized by the persistence of thromboembolic obstructing the pulmonary arteries as an organized tissue and the presence of a variable small vessel arteriopathy. The consequence is an increase in pulmonary vascular resistance resulting in progressive right heart failure. CTEPH is classified as group IV pulmonary hypertension according to the WHO classification of pulmonary hypertension. CTEPH is defined as precapillary pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mmHg with a pulmonary capillary wedge pressure ≤ 15 mmHg) associated with mismatched perfusion defects on ventilation-perfusion lung scan and signs of chronic thromboembolic disease on computed tomography pulmonary angiogram and/or conventional pulmonary angiography, in a patient who received at least 3 months of therapeutic anticoagulation. CTEPH as a direct consequence of symptomatic pulmonary embolism (PE) is rare, and a significant number of CTEPH cases develop in the absence of history of PE. Thus, CTEPH should be considered in any patient with unexplained PH. Splenectomy, chronic inflammatory conditions such as inflammatory bowel disease, indwelling catheters and cardiac pacemakers have been identified as associated conditions increasing the risk of CTEPH. Ventilation-perfusion scan (V/Q) is the best test available for establishing the thromboembolic nature of PH. When CTEPH is suspected, patients should be referred to expert centres where pulmonary angiography, right heart catheterization and high-resolution CT scan will be performed to confirm the diagnosis and to assess the operability. Pulmonary endarterectomy (PEA) remains the gold standard treatment for CTEPH when organized thrombi involve the main, lobar or segmental arteries. This operation should only be performed by experienced surgeons in specialized centres. For inoperable patients, current ESC/ERS guidelines for the

  14. Perspectives on research in hypertension.

    PubMed

    Seedat, Y K

    2009-01-01

    This is a review of my published research on hypertension over 45 years on the three main racial groups residing in KwaZulu-Natal and its main city Durban. These three groups are blacks - mainly Zulu, whites and Indians. The research focused mainly on epidemiology, determinants of the aetiology of hypertension, clinical features, varying responses to hypotensive agents among the racial groups, complications that result from hypertension and the control of hypertension. PMID:19287815

  15. Association between pregnancy-related hypertension and severity of hypertension.

    PubMed

    Moreira, L B; Gus, M; Nunes, G; Gonçalves, C B C; Martins, J; Wiehe, M; Fuchs, F D

    2009-06-01

    Hypertension in pregnancy is an emerging sex-specific risk factor for cardiovascular disease and may lead to more severe hypertension after pregnancy. The objectives of this study were to investigate the frequency of pregnancy-related hypertension among patients referred to a hypertension clinic and its association with the severity of hypertension and evidence of end-organ damage. In this cross-sectional study, women with hypertension were submitted to a systematic clinical evaluation. The occurrence of pregnancy-related hypertension was investigated by questionnaire. The association between pregnancy-related hypertension and severity of hypertension (stage 2 according to Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII)) and end-organ damage was assessed in a logistic regression model. The mean age, systolic and diastolic blood pressure and body mass index (BMI) of the 768 women examined were 51.6+/-12.7 years, 158.2+/-26.6 mm Hg, 93.8+/-14.3 mm Hg and 29.4+/-5.6 kg/m(2), respectively. The proportion of women with pregnancy-related hypertension was 32.9%. It was significantly associated with hypertension at stage 2 (OR: 1.60, 95% CI: 1.14-2.24; P=0.01) after controlling for confounders. The occurrence of a pregnancy-related hypertension was not associated with evidence of optic fundi abnormalities, left ventricular hypertrophy or abnormalities in kidney function. In conclusion, pregnancy-related hypertension is frequent in women referred to a hypertension clinic, and is associated with severe hypertension but not with evidence of end-organ damage. PMID:19020534

  16. Pulmonary hypertension caused by pulmonary venous hypertension

    PubMed Central

    2014-01-01

    Abstract The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility. PMID:25610595

  17. The Power of Positioning: On the Normalisation of Gender, Race/Ethnicity, Nation and Class Positions in a Swedish Social Work Textbook

    ERIC Educational Resources Information Center

    Fahlgren, Siv; Sawyer, Lena

    2011-01-01

    This article presents a feminist reading of a Swedish social work academic textbook as a case study. We use a discourse analytic approach and positioning theory, focusing on author positions through different story lines. The aim is to make visible how differences are created and positions of the author/reader normalised in terms of gender,…

  18. Differential effectiveness of tianeptine, clonidine and amitriptyline in blocking traumatic memory expression, anxiety and hypertension in an animal model of PTSD.

    PubMed

    Zoladz, Phillip R; Fleshner, Monika; Diamond, David M

    2013-07-01

    Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents. PMID:23318688

  19. Reprogramming: A Preventive Strategy in Hypertension Focusing on the Kidney

    PubMed Central

    Tain, You-Lin; Joles, Jaap A.

    2015-01-01

    Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies. PMID

  20. [Hypertensive emergency and urgence].

    PubMed

    Gegenhuber, Alfons; Lenz, Kurt

    2003-12-01

    DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by a massive, acute rise in blood pressure. Patients with underlying hypertensive disease usually have an increase in systolic blood pressure values > 220 mmHg and diastolic values > 120 mmHg. The severity of the condition, however, is not determined by the absolute blood pressure level but by the magnitude of the acute increase in blood pressure. Thus, in the presence of primarily normotensive baseline values (such as those in eclampsia), even a systolic blood pressure > 170 mmHg may lead to a life-threatening condition. The most important causes are non-compliance (reduction or interruption of therapy), inadequate therapy, endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs). The management of this condition greatly depends on whether the patient has a hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis without organ manifestation (hypertensive urgency). By documenting the medical history, the medical status and by simple diagnostic procedures, the differential diagnosis can be established at the emergency site within a very short period of time. In the absence of organ manifestations (hypertensive urgency) the patient may have non-specific symptoms such as palpitations, headache, malaise and a general feeling of illness in addition to the increase in blood pressure. In a hypertensive urgency the patient's blood pressure should not be reduced within a few minutes but within a period of 24 to 48 hours. Such adjustment can be achieved on an out-patient basis, however, only if the patient can be followed up adequately for early detection of a renewed attack. In the absence of follow-up facilities, the patient's blood pressure should be reduced over a period of 4 to 6 hours, if necessary in an out-patient emergency service. While intravenous medication is given preference when a rapid effect is desired, oral medication may be used for

  1. Nocturnal blood pressure profiles among normotensive, controlled hypertensive and refractory hypertensive subjects

    PubMed Central

    Friedman, Oded; Logan, Alexander G

    2009-01-01

    BACKGROUND: Nocturnal blood pressure abnormalities are independently associated with an increased risk of death and cardiovascular disease. It is unclear, however, whether they are related to the presence or severity of hypertension. OBJECTIVES: To determine and compare the prevalence of sleep pattern disturbances in normotensive (NT) and hypertensive patients. METHODS: The present cross-sectional study assessed the nocturnal blood pressure profiles from 24 h ambulatory blood pressure monitoring of refractory hypertensive (RH) (n=26), controlled hypertensive (CH) (n=52) and NT (n=52) subjects who were matched for age, sex and body mass index. Results are expressed as mean ± SD or proportion, as appropriate. RESULTS: During sleep, the percentage fall in mean arterial pressure was 15.1±6.1% in the NT group, 11.5±7.0% in the CH group and 7.7±7.7% in the RH group (P<0.0001). The corresponding proportions of nondipping were 25.0%, 42.3% and 61.5%, respectively (P=0.006), and those of nocturnal hypertension were 9.6%, 23.1% and 84.6%, respectively (P<0.0001). All pairwise comparisons of nocturnal blood pressure fall were significant. The proportion of subjects in the RH group who experienced a rise in nocturnal blood pressure (19.2%) was significantly greater than the proportions in the NT and CH groups (P=0.001), as was the proportion of subjects with nocturnal hypertension (P<0.0001). There was less extreme dipping in RH, although the difference was not statistically significant (P=0.08). CONCLUSIONS: A significantly higher prevalence of nondipping, nocturnal hypertension and nocturnal blood pressure rising in RH was demonstrated. These sleep disturbances or independently, their cause, may account for the difficulties in attaining blood pressure control. PMID:19746250

  2. Gender Differences in Hypertension and Hypertension Awareness Among Young Adults

    PubMed Central

    EVERETT, BETHANY; ZAJACOVA, ANNA

    2016-01-01

    Previous research has shown that men have higher levels of hypertension and lower levels of hypertension awareness than women, but it remains unclear if these differences emerge among young adults. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examines gender differences in hypertension and hypertension awareness among U.S. young adults, with special focus on factors that may contribute to observed disparities (N = 14,497). Our results show that the gender disparities in hypertension status were already evident among men and women in their twenties: women were far less likely to be hypertensive compared to men (12% vs. 27%). The results also reveal very low levels of hypertension awareness among young women (32% of hypertensive women were aware of their status) and even lower levels among men (25%). Finally, this study identifies key factors that contribute to these observed gender disparities. In particular, health care use, while not related to the actual hypertension status, fully explains the gender differences in hypertension awareness. The findings thus suggest that regular medical visits are critical for improving hypertension awareness among young adults and reducing gender disparities in cardiovascular health. PMID:25879259

  3. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

    PubMed Central

    Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

  4. Hypertension in adolescents.

    PubMed

    Aglony, Marlene; Acevedo, Monica; Ambrosio, Giuseppe

    2009-12-01

    In adults, hypertension has long been perceived as a public health problem. By contrast, its impact in childhood is far less appreciated. In fact, quite often, high blood pressure in children is not even diagnosed. Blood pressure is a vital sign that is routinely obtained during a physical examination of adults, but only very seldom in children. The diagnosis of hypertension in children is complicated because 'normal' blood pressure values vary with age, sex and height. As a consequence, almost 75% of the cases of arterial hypertension and 90% of the cases of prehypertension in children and adolescents are currently undiagnosed. Furthermore, adolescence hypertension is increasing in prevalence as the prevalence of pediatric obesity has increased. Ambulatory blood pressure monitoring is a useful method for risk evaluation in adolescents. In addition to being viewed as an important cardiovascular risk factor in adolescents, elevated blood pressure should prompt a thorough search for other modifiable risk factors that, if treated, might reduce teenagers' risk of developing cardiovascular disease in adulthood. Thus, assessing blood pressure values in children represents one of the most important measurable markers of cardiovascular risk later in life and a major step in preventive medicine. PMID:19954321

  5. Carvedilol in hypertension treatment

    PubMed Central

    Stafylas, Panagiotis C; Sarafidis, Pantelis A

    2008-01-01

    Although β-blockers have been previously shown to effectively reduce blood pressure (BP) and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of β-blockers. Carvedilol, a vasodilating non-cardioselective β-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional β-blocker therapy. In contrast with conventional β-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional β-blockers, attempting to examine the potential use of this agent for hypertension treatment. PMID:18629377

  6. High Blood Pressure (Hypertension)

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women High Blood Pressure (Hypertension) Share Tweet Linkedin Pin it More sharing options ... En Español Who is at risk? How is high blood pressure treated? Understanding your blood pressure: What do the ...

  7. Idiopathic pulmonary arterial hypertension.

    PubMed

    Souza, Rogerio; Jardim, Carlos; Humbert, Marc

    2013-10-01

    Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension, is a rare disease (incidence and prevalence rates of approximately one and six cases per million inhabitants, respectively) with different clinical phenotypes. A group of diverse conditions manifest pulmonary arterial hypertension (PAH) and share similar pathological and/or clinical findings with IPAH. By definition, IPAH is diagnosed only after alternative diagnoses have been ruled out. Extensive investigation is needed to determine if PAH is associated with thyroid diseases, infectious diseases, autoimmune conditions, exposure to certain drugs (particularly anorexigens), certain genetic mutations, and so on. The presence of genetic abnormalities and risk factors (such as specific drug exposures) reinforces the "multiple hit" concept for the development of pulmonary hypertension. Fortunately, within the past two decades, therapeutic options have become available for IPAH, resulting in improved survival and clinical outcomes. At least seven different compounds have been registered for PAH treatment. However, even with aggressive PAH-specific therapy, mortality rates remain high (∼40% at 5 years). Given the high mortality rates, the use of combinations of agents that work by different pathways has been advocated (either as "add-on" therapy or initial "up front" therapy). Further, new therapeutic agents and treatment strategies are on the near horizon, aiming to further improve survival from the remarkable progress already seen. PMID:24037625

  8. Pregnancy-Induced Hypertension

    MedlinePlus

    ... upper arm. Then they listen to your blood flow with a stethoscope. High blood pressure (also called hypertension) occurs when your ... is not a good idea if you have high blood pressure during pregnancy. Your body needs salt to keep up the flow of fluid in your body, so you need ...

  9. Hypertension, a health economics perspective.

    PubMed

    Alcocer, Luis; Cueto, Liliana

    2008-06-01

    The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment. PMID:19124418

  10. Cognitive function in hypertensive children.

    PubMed

    Lande, Marc B; Kupferman, Juan C

    2015-01-01

    Young hypertensive adults demonstrate decreased performance on neurocognitive testing compared with that of normotensive controls. There is emerging, preliminary evidence that children with hypertension also manifest cognitive differences when compared to normotensive controls. These preliminary studies consist mostly of database and single-center studies that focus primarily on differences in neurocognitive test performance and differences in cerebrovascular reactivity between hypertensive and normotensive subjects. Lessons from the literature on cognition in adult hypertensives and experience from the preliminary studies in children informed the design of a current, multicenter, ongoing study of cognition in children with primary hypertension. PMID:25432900

  11. Impaired Neovascularization and Reduced Capillary Supply in the Malignant vs. Non-malignant Course of Experimental Renovascular Hypertension.

    PubMed

    Hartner, Andrea; Jagusch, Lisa; Cordasic, Nada; Amann, Kerstin; Veelken, Roland; Jacobi, Johannes; Hilgers, Karl F

    2016-01-01

    Malignant hypertension develops in some cases of hypertension but not in others. We hypothesized that an impaired neovascularization and a reduced capillary supply characterizes the malignant course of experimental hypertension. Two-kidney, one-clip renovascular hypertension was induced in rats; controls (sham) were sham operated. To distinguish malignant hypertension from non-malignant hypertension, we considered two factors: weight loss, and the number of typical vascular lesions (onion skin lesions and fibrinoid necroses) per kidney section of the nonclipped kidney. Animals in the upper half for both criteria were defined as malignant hypertensives. After 5 weeks, mean arterial blood pressure was elevated to the same degree in malignant hypertension and non-malignant hypertension whereas plasma renin and aldosterone were significantly higher in malignant hypertensives. The expression of plasminogen activator inhibitor-1 was elevated (up to 14-fold) in non-malignant but significantly more increased (up to 36-fold) in malignant hypertensive rats, compared to sham. As a bioassay for neovascularization, the area of granulation tissue ingrowth in polyvinyl discs (implanted subcutaneously) was reduced in malignant hypertension compared to non-malignant hypertension and sham, while there was no difference between non-malignant hypertension and sham. The number of renal and left ventricular capillaries was significantly lower in malignant hypertension compared to non-malignant hypertension, as was the number of proliferating endothelial cells. We conclude that an impaired neovascularization and capillarization occurs in malignant renovascular hypertension but not in the non-malignant course of the disease despite comparable blood pressure levels. This might contribute to the unique vascular lesions and progressive target organ damage observed in malignant hypertension. PMID:27625610

  12. Impaired Neovascularization and Reduced Capillary Supply in the Malignant vs. Non-malignant Course of Experimental Renovascular Hypertension

    PubMed Central

    Hartner, Andrea; Jagusch, Lisa; Cordasic, Nada; Amann, Kerstin; Veelken, Roland; Jacobi, Johannes; Hilgers, Karl F.

    2016-01-01

    Malignant hypertension develops in some cases of hypertension but not in others. We hypothesized that an impaired neovascularization and a reduced capillary supply characterizes the malignant course of experimental hypertension. Two-kidney, one-clip renovascular hypertension was induced in rats; controls (sham) were sham operated. To distinguish malignant hypertension from non-malignant hypertension, we considered two factors: weight loss, and the number of typical vascular lesions (onion skin lesions and fibrinoid necroses) per kidney section of the nonclipped kidney. Animals in the upper half for both criteria were defined as malignant hypertensives. After 5 weeks, mean arterial blood pressure was elevated to the same degree in malignant hypertension and non-malignant hypertension whereas plasma renin and aldosterone were significantly higher in malignant hypertensives. The expression of plasminogen activator inhibitor-1 was elevated (up to 14-fold) in non-malignant but significantly more increased (up to 36-fold) in malignant hypertensive rats, compared to sham. As a bioassay for neovascularization, the area of granulation tissue ingrowth in polyvinyl discs (implanted subcutaneously) was reduced in malignant hypertension compared to non-malignant hypertension and sham, while there was no difference between non-malignant hypertension and sham. The number of renal and left ventricular capillaries was significantly lower in malignant hypertension compared to non-malignant hypertension, as was the number of proliferating endothelial cells. We conclude that an impaired neovascularization and capillarization occurs in malignant renovascular hypertension but not in the non-malignant course of the disease despite comparable blood pressure levels. This might contribute to the unique vascular lesions and progressive target organ damage observed in malignant hypertension. PMID:27625610

  13. Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats.

    PubMed

    Zhu, Jun; Zhang, Yantao; Yang, Changhai

    2015-02-01

    Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms. PMID:25352064

  14. Hemorheology in complicated hypertension.

    PubMed

    Cicco, G; Vicenti, P; Stingi, G D; Tarallo; Pirrelli, A

    1999-01-01

    During essential and secondary arterial hypertension it is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as an increase in blood viscosity or the formation of the red blood cell "rouleaux" which favour an increase in peripheral resistance and can cause or worsen arterial hypertension. We studied 21 healthy subjects (11 male and 10 female aged 42 +/- 4) and 26 hypertensive subjects (14 male and 12 female aged 49 +/- 3). The patients were non smokers and non suffering from respiratory or haemathological pathologies. They were not undergoing antihypertensive or vasodilatory pharmaceutical treatment. The patients suffered from mild hypertension (II WHO) with Peripheral Occlusive Arterial Disease (POAD II "a" acc. to Leriche-Fontaine class.). The patients showed an increase in cholesterolaemia (6.42 +/- 0.81 mmol/l) and trygliceridaemia (2.73 +/- 0.09 mmol/l) at an average level. The patients were studied in standard conditions with a constant temperature of 22 degrees C. We measured SBP, DBP, MBP, and the HR. We also measured the elongation index (EI) (with shear stress range 0.30 to 30 pascals) using LORCA, acc. to Hardeman method (1994), in order to study the erythrocyte deformability and aggregation kinetics in dynamic condition. To evaluate deformability in static conditions we calculated the Erythrocyte Morphologic Index (EMI), acc. to Forconi method, via the bowl/discocyte ratio (for 100 red blood cells fixed in glutaraldehyde at 0.3% and observed with an optical microscope under immersion in glycerol). Peripheral oxygenation was taken transcutaneously (TcpO2). To establish the level of vascular disease we used the Regional Perfusion Index (RPI = TcpO2 foot/TcpO2 subclavean) and doppler guided Winsor Index (WI). The Student "t" test and linear regression were used for the statistical analysis. Our data confirm a reduction in peripheral tissue oxygenation in

  15. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke.

    PubMed

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood-brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  16. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

    PubMed Central

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood–brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte–leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  17. The role of bicycle sharing systems in normalising the image of cycling: An observational study of London cyclists

    PubMed Central

    Goodman, Anna; Green, Judith; Woodcock, James

    2014-01-01

    Bicycle sharing systems are increasingly popular around the world and have the potential to increase the visibility of people cycling in everyday clothing. This may in turn help normalise the image of cycling, and reduce perceptions that cycling is ‘risky’ or ‘only for sporty people’. This paper sought to compare the use of specialist cycling clothing between users of the London bicycle sharing system (LBSS) and cyclists using personal bicycles. To do this, we observed 3594 people on bicycles at 35 randomly-selected locations across central and inner London. The 592 LBSS users were much less likely to wear helmets (16% vs. 64% among personal-bicycle cyclists), high-visibility clothes (11% vs. 35%) and sports clothes (2% vs. 25%). In total, 79% of LBSS users wore none of these types of specialist cycling clothing, as compared to only 30% of personal-bicycle cyclists. This was true of male and female LBSS cyclists alike (all p>0.25 for interaction). We conclude that bicycle sharing systems may not only encourage cycling directly, by providing bicycles to rent, but also indirectly, by increasing the number and diversity of cycling ‘role models’ visible. PMID:25568838

  18. Speech Perception and Localisation with SCORE Bimodal: A Loudness Normalisation Strategy for Combined Cochlear Implant and Hearing Aid Stimulation

    PubMed Central

    Francart, Tom; McDermott, Hugh

    2012-01-01

    A significant fraction of newly implanted cochlear implant recipients use a hearing aid in their non-implanted ear. SCORE bimodal is a sound processing strategy developed for this configuration, aimed at normalising loudness perception and improving binaural loudness balance. Speech perception performance in quiet and noise and sound localisation ability of six bimodal listeners were measured with and without application of SCORE. Speech perception in quiet was measured either with only acoustic, only electric, or bimodal stimulation, at soft and normal conversational levels. For speech in quiet there was a significant improvement with application of SCORE. Speech perception in noise was measured for either steady-state noise, fluctuating noise, or a competing talker, at conversational levels with bimodal stimulation. For speech in noise there was no significant effect of application of SCORE. Modelling of interaural loudness differences in a long-term-average-speech-spectrum-weighted click train indicated that left-right discrimination of sound sources can improve with application of SCORE. As SCORE was found to leave speech perception unaffected or to improve it, it seems suitable for implementation in clinical devices. PMID:23115622

  19. Literacy and motivation for the prevention and control of hypertension among female community health volunteers: a qualitative study from Nepal

    PubMed Central

    Neupane, Dinesh; Mclachlan, Craig S.; Gautam, Rupesh; Mishra, Shiva Raj; Thorlund, Michael; Schlütter, Mette; Kallestrup, Per

    2015-01-01

    Background The prevalence of hypertension is increasing in Nepal. Thus, there is a need for a programme to improve primary healthcare. One possibility is to assign prevention, diagnosis, and treatment of hypertension to female community health volunteers (FCHVs). Objective To assess literacy and motivation to be involved in a hypertension prevention and control programme in Nepal among FCHVs. Design Five focus group discussions (FGDs) were conducted with a total of 69 FCHVs in Lekhnath municipality, Kaski district, Nepal. Seven themes were developed on the basis of data collection: 1) knowledge about hypertension; 2) risk factors of hypertension; 3) prevention and control of hypertension; 4) access to treatment for hypertension in the community; 5) learning about blood pressure measurement; 6) ability to raise blood pressure awareness in the community; 7) possible challenges for their future involvement. Data were analysed using the thematic analysis approach. Results FCHVs have some knowledge about diagnosis, risk factors, and complications of hypertension. General unanimity was observed in the understanding that hypertension and risk factors needed to be addressed. The willingness of FCHVs to contribute to prevention, control, and management was strong, and they were confident that with some basic training they could obtain skills in hypertension management. Conclusions Despite limited knowledge about hypertension, FCHVs expressed willingness and readiness to be trained in hypertension management. This study supports the possibility of involving FCHVs in prevention and control of hypertension in Nepal. PMID:26679406

  20. Hypertension: the missing WNKs.

    PubMed

    Dbouk, Hashem A; Huang, Chou-Long; Cobb, Melanie H

    2016-07-01

    The With no Lysine [K] (WNK) family of enzymes are central in the regulation of blood pressure. WNKs have been implicated in hereditary hypertension disorders, mainly through control of the activity and levels of ion cotransporters and channels. Actions of WNKs in the kidney have been heavily investigated, and recent studies have provided insight into not only the regulation of these enzymes but also how mutations in WNKs and their interacting partners contribute to hypertensive disorders. Defining the roles of WNKs in the cardiovascular system will provide clues about additional mechanisms by which WNKs can regulate blood pressure. This review summarizes recent developments in the regulation of the WNK signaling cascade and its role in regulation of blood pressure. PMID:27009339

  1. Hypertension in perspective

    PubMed Central

    Terpstra, W.F.; Zijlstra, F.

    2005-01-01

    Decisions about the management of hypertensive patients should not be based on the level of blood pressure alone, but also on the presence of other risk factors, target organ damage and cardiovascular and renal disease. The results of echocardiography and carotid ultrasonography aids in the stratification of absolute cardiovascular risk as recently advocated by the guidelines of the European Society of Hypertension 2003. Therefore, the detection of target organ damage by ultrasound techniques allows an accurate identification of high-risk patients. Cardiovascular risk stratification only based on a simple routine work-up can often underestimate overall risk, thus leading to a potentially inadequate therapeutic management especially of low-medium risk patients. PMID:25696486

  2. [Hypertensive Disorders in Pregnancy].

    PubMed

    Middeke, Martin

    2016-09-01

    In pregnancy, both mother and fetus benefit from blood pressure in normal ranges. There is discrepancy in the normenclature and thresholds for classification of hypertension in pregnancy and for initiation of antihypertensive treatment in different international guidelines. Systolic and diastolic blood pressure values that are associated with normal outcome are notably lower than any recommended treatment threshold in pregnancy. Tight blood pressure control under 85 mmHg diastolic is save and significantly prevents severe maternal hypertension as could be demonstrated in CHIPS. Close blood pressure monitoring comprising modern methods and devices including telemonitoring allows early recognition of risk developments and optimal guidance of antihypertensive therapy starting early in pregnancy. Only a few pharmacological substances are suitable for antihypertensive treatment in pregnancy. PMID:27598915

  3. An update on hypertensive emergencies and urgencies.

    PubMed

    Muiesan, Maria Lorenza; Salvetti, Massimo; Amadoro, Valentina; di Somma, Salvatore; Perlini, Stefano; Semplicini, Andrea; Borghi, Claudio; Volpe, Massimo; Saba, Pier Sergio; Cameli, Matteo; Ciccone, Marco Matteo; Maiello, Maria; Modesti, Pietro Amedeo; Novo, Salvatore; Palmiero, Pasquale; Scicchitano, Pietro; Rosei, Enrico Agabiti; Pedrinelli, Roberto

    2015-05-01

    Severe acute arterial hypertension is usually defined as 'hypertensive crisis', although 'hypertensive emergencies' or 'hypertensive urgencies', as suggested by the Joint National Committee and the European Society of Hypertension, have completely different diagnostic and therapeutic approaches.The prevalence and demographics of hypertensive emergencies and urgencies have changed over the last four decades, but hypertensive emergencies and urgencies are still associated with significant morbidity and mortality.Different scientific societies have repeatedly produced up-to-date guidelines; however, the treatment of hypertensive emergencies and urgencies is still inappropriate, with potential clinical implications.This review focuses on hypertensive emergencies and urgencies management and treatment, as suggested by recent data. PMID:25575271

  4. Express

    Integrated Risk Information System (IRIS)

    Express ; CASRN 101200 - 48 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  5. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  6. Drug Treatment of Hypertension

    PubMed Central

    Ryan, Douglas R.

    1991-01-01

    Hypertension is an important contributor to cardiovascular disease, which accounts for about half of all deaths in Western societies. Proper control of elevated blood pressure is therefore important. Support has grown for an approach to care in which antihypertensive drug therapy is individually tailored for each patient. Management strategy based on this approach is discussed, and the advantages and disadvantages of the various antihypertensive agents are reviewed. PMID:21229011

  7. Classification of Pulmonary Hypertension.

    PubMed

    Oudiz, Ronald J

    2016-08-01

    The classification of pulmonary hypertension (PH) is an attempt to define subtypes of PH based on clinical presentation, underlying physiology, and treatment implications. Five groups of PH have been defined, and the classification scheme has been refined over the years to guide clinicians in the diagnosis and management of PH. Understanding the classification of PH is paramount before embarking on a work-up of patients with PH or suspected PH because treatment and outcome can vary greatly. PMID:27443133

  8. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  9. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats.

    PubMed

    Li, Yali; Liu, Jian; Gao, Dengfeng; Wei, Jin; Yuan, Haifeng; Niu, Xiaolin; Zhang, Qiaojun

    2016-03-01

    The aim of the present study was to investigate the age‑related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase‑3). In addition, the expression of PPAR‑γ and Bcl‑2 were progressively reduced with increasing age in the SHR group. The 32 and 64‑week‑old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro‑apoptotic proteins compared with age‑matched WKY rats, which was accompanied by reduced expression of PPAR‑γ. Compared with the 16 and 32‑week‑old WKY group, the 64‑week‑old WKY rats exhibited increased oxidative stress and pro‑apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR‑γ may contribute to the age‑related brain damage in SHRs. PMID:26846626

  10. Portal hypertensive enteropathy

    PubMed Central

    Mekaroonkamol, Parit; Cohen, Robert; Chawla, Saurabh

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentation and grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed. PMID:25729469

  11. [Chronic thromboembolic pulmonary hypertension].

    PubMed

    Zonzin, Pietro; Vizza, Carmine Dario; Favretto, Giuseppe

    2003-10-01

    Chronic thromboembolic pulmonary hypertension is due to unresolved or recurrent pulmonary embolism. In the United States the estimated prevalence is 0.1-0.5% among survived patients with pulmonary embolism. The survival rate at 5 years was 30% among patients with a mean pulmonary artery pressure > 40 mmHg at the time of diagnosis and only 10% among those with a value > 50 mmHg. The interval between the onset of disturbances and the diagnosis may be as long as 3 years. Doppler echocardiography permits to establish the diagnosis of pulmonary hypertension. Radionuclide scanning determines whether pulmonary hypertension has a thromboembolic basis. Right heart catheterization and pulmonary angiography are performed in order to establish the extension and the accessibility to surgery of thrombi and to rule out other causes. The surgical treatment is thromboendarterectomy. A dramatic reduction in the pulmonary vascular resistance can be achieved; corresponding improvements in the NYHA class--from class III or IV before surgery to class I-II after surgery--are usually observed. Patients who are not considered candidates for thromboendarterectomy may be considered candidates for lung transplantation. PMID:14664293

  12. Hypertension in the elderly.

    PubMed

    Coope, J

    1987-08-01

    Hypertension is a common finding in patients aged over 60 years, but the following questions need answering. How dangerous is it? Will lowering the blood pressure reduce the attendant risks? What is the 'cost' of such treatment in terms of side effects, drug-induced disease and health service finance? Two recently completed trials throw light on these problems: EWPHE (European Working Party on Hypertension in the Elderly), a European study based on hospital-clinic attenders, using a diuretic backed up with methyldopa; and HEP (randomized trial of treatment of Hypertension in Elderly Patients in Primary Care), based on general-practice screening in England and Wales using atenolol and bendrofluazide. The results of these trials were compared and the findings were broadly similar in the two studies. Some of the differences may be due to the different selection of patients. It is concluded that elderly patients with sustained blood pressures greater or equal to 170/90 mmHg would benefit from treatment by substantial reduction of stroke. Diuretics or beta-blockers, alone or together, are acceptable treatments in elderly subjects. PMID:3312529

  13. Hypertension in Chronic Glomerulonephritis.

    PubMed

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  14. Management of hypertension emergencies.

    PubMed

    Elliott, William J

    2003-12-01

    Although they have become less common, hypertensive emergencies occur with an incidence of approximately 1 to 2/100,000 people per year. Our knowledge about this problem, its pathophysiology, risk factors, and appropriate treatment options has expanded during the past decade. A hypertensive emergency can be declared when an elevated blood pressure is associated with acute target-organ damage. Rapid evaluation and treatment (typically with an intravenously administered agent) should be instituted, usually in an intensive care unit setting, and the patient should be observed carefully during acute blood-pressure lowering. When properly treated, the prognosis for these patients is not nearly as dismal as it was more than 60 years ago, and the initial level of function of target organs (brain, heart, kidneys) is more indicative of an emergency than the actual level of blood pressure. Therapeutic options include the time-tested sodium nitroprusside (which has toxic metabolic products and is contraindicated in pregnancy, tobacco amblyopia, and Leber's optic atrophy); fenoldopam mesylate; and nicardipine. When properly treated, "malignant hypertension" need be considered malignant no longer. PMID:14594569

  15. Managing hypertension by polyphenols.

    PubMed

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. PMID:25714729

  16. Hypertension in the elderly.

    PubMed

    Robles, Nicolas R; Macias, Juan F

    2015-01-01

    Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. Aging is an inevitable part of life and brings along two inconvenient events: physiologic decline and disease state. High blood pressure (HBP) is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. It is a significant and often asymptomatic chronic disease, which requires optimal control and persistent adherence to prescribed medication to reduce the risks of cardiovascular, cerebrovascular and renal disease. Hypertension in the elderly patients represents a management dilemma to geriatric and cardiovascular specialists and other practitioners. Furthermore, with the wide adoption of multiple drug strategies targeting subgroups of hypertensive patients with specific risk conditions to lower blood pressure (BP), difficult questions arise about how aggressive treatment of elderly patients should be. The purpose of the following chapter article is to review the pathophysiology of aging as well as the epidemiology and the clinical assessment of high blood pressure (HBP) in older people. PMID:25761101

  17. Pulmonary Hypertension in Cardiac Surgery

    PubMed Central

    Denault, André; Deschamps, Alain; Tardif, Jean-Claude; Lambert, Jean; Perrault, Louis

    2010-01-01

    Pulmonary hypertension is an important prognostic factor in cardiac surgery associated with increased morbidity and mortality. With the aging population and the associated increase severity of illness, the prevalence of pulmonary hypertension in cardiac surgical patients will increase. In this review, the definition of pulmonary hypertension, the mechanisms and its relationship to right ventricular dysfunction will be presented. Finally, pharmacological and non-pharmacological therapeutic and preventive approaches will be presented. PMID:21286273

  18. Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension

    PubMed Central

    Nikkari, Seppo T.; Määttä, Kirsi M.; Kunnas, Tarja A.

    2015-01-01

    Abstract Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort. This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression. At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08–2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20–12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1

  19. Pharmacologic Treatment of Pediatric Hypertension.

    PubMed

    Dhull, Rachita S; Baracco, Rossana; Jain, Amrish; Mattoo, Tej K

    2016-04-01

    Prevalence of hypertension is increasing in children and adolescents. Uncontrolled hypertension in children not only causes end organ damage but also increases the risk of adult hypertension and cardiovascular disease. Clinical trials have proven efficacy of antihypertensive medications in children. These medications are well tolerated by children with acceptable safety profile. The choice of agent is usually driven by underlying etiology of hypertension, profile of its side effects, and clinician's preference. This article will review currently available pediatric data on mechanism of action, common adverse effects, pediatric indication, recent clinical trial, and newer drugs in the common classes of antihypertensive medications. PMID:27048353

  20. Vascular Inflammatory Cells in Hypertension

    PubMed Central

    Harrison, David G.; Marvar, Paul J.; Titze, Jens M.

    2012-01-01

    Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease. PMID:22586409

  1. Hyperuricemia and uncontrolled hypertension in treated hypertensive patients

    PubMed Central

    Cho, Jaelim; Kim, Changsoo; Kang, Dae Ryong; Park, Jeong Bae

    2016-01-01

    Abstract Previous epidemiological studies have suggested that uric acid is an independent risk factor for incident hypertension, whereas few studies have evaluated the effect of hyperuricemia on blood pressure control in hypertensive patients. We investigated whether hyperuricemia predicts uncontrolled hypertension through a large-scale prospective cohort study with hypertensive patients treated with fimasartan in the Republic of Korea (the Kanarb–Metabolic Syndrome study). Of the 10,601 hypertensive patients who were recruited from 582 private clinics and 11 university hospitals at baseline, 7725 completed the follow-up after 3 months of fimasartan medication, and 6506 were included in the analysis after excluding those with missing values. We estimated the risk of uncontrolled hypertension after 3 months (≥130/80 mm Hg in those with diabetes or chronic renal failure and ≥140/90 mm Hg in the remaining patients) related with baseline hyperuricemia (serum uric acid ≥7 mg/dL in males ≥6 mg/dL in females) using multiple logistic regression models. Hyperuricemia increased the risk of uncontrolled hypertension after 3 months of fimasartan medication (odds ratio, 1.247; 95% confidence interval, 1.063–1.462). Males in the highest quartile of uric acid level were at a 1.322 (95% confidence interval, 1.053–1.660) times higher risk of uncontrolled hypertension in reference to the lowest quartile; the same analyses in females were not significant. Patients without metabolic syndrome had significantly higher odds of uncontrolled hypertension with hyperuricemia (odds ratio, 1.328; 95% confidence interval, 1.007–1.751). Hyperuricemia predicted uncontrolled hypertension even after 3 months of fimasartan treatment in hypertensive patients. PMID:27428212

  2. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  3. Home point-of-care international normalised ratio monitoring sustained by a non-selective educational program in children.

    PubMed

    Bajolle, Fanny; Lasne, Dominique; Elie, Caroline; Cheurfi, Radhia; Grazioli, Aurélie; Traore, Maladon; Souillard, Patrick; Boudjemline, Younes; Jourdain, Patrick; Bonnet, Damien

    2012-10-01

    Adverse events related to vitamin K antagonist (VKA) therapy might be reduced by point-of-care international normalised ratio (POC INR) monitoring supported by an education program (EP). Our aim was to evaluate the efficacy of a non-selective VKA paediatric EP (regardless of the social, economic, educational or linguistic levels) by analysing the time spent in the therapeutic range (TTR), VKA adverse events and compliance to treatment, and INR control prescriptions. The EP was modified from the pediatric EP previously described but improved by a specifically devised child-focused game. One hundred four consecutive children (median age 8 years) receiving VKA were included in a standardised EP. Patients were in self-testing, and dose adjustments were made by a single physician for three tolerance ranges according to the underlying disease: [2.5-4], [1.8-3.2], and [1.5-2.5]. The median follow-up was 481 days [70-1,001]. The overall TTR was 81.4% [36-100]. The TTR were 74%, 85.6% and 89% for the ranges [2.5-4], [1.8-3.2], and [1.5-2.5], respectively. These results were sustainable during the study period. Only one serious VKA adverse event was recorded. The median number of POC INR tests was 2.5 [1.6-5.7] INR per patient and month. Patients/families performed POC INR when requested in 86.9% of the cases. More than 90% of the families found the EP supportive and wished to follow a long-term reinforcement program. In conclusion, this non-selective child-focused EP for VKA therapy, strongly supported by our dedicated game, is useful in maintaining efficacy, safety and compliance to anticoagulation and its monitoring. PMID:22955724

  4. Comparative analysis of normalised difference spectral indices derived from MODIS for detecting surface water in flooded rice cropping systems.

    PubMed

    Boschetti, Mirco; Nutini, Francesco; Manfron, Giacinto; Brivio, Pietro Alessandro; Nelson, Andrew

    2014-01-01

    Identifying managed flooding in paddy fields is commonly used in remote sensing to detect rice. Such flooding, followed by rapid vegetation growth, is a reliable indicator to discriminate rice. Spectral indices (SIs) are often used to perform this task. However, little work has been done on determining which spectral combination in the form of Normalised Difference Spectral Indices (NDSIs) is most appropriate for surface water detection or which thresholds are most robust to separate water from other surfaces in operational contexts. To address this, we conducted analyses on satellite and field spectral data from an agronomic experiment as well as on real farming situations with different soil and plant conditions. Firstly, we review and select NDSIs proposed in the literature, including a new combination of visible and shortwave infrared bands. Secondly, we analyse spectroradiometric field data and satellite data to evaluate mixed pixel effects. Thirdly, we analyse MODIS data and Landsat data at four sites in Europe and Asia to assess NDSI performance in real-world conditions. Finally, we test the performance of the NDSIs on MODIS temporal profiles in the four sites. We also compared the NDSIs against a combined index previously used for agronomic flood detection. Analyses suggest that NDSIs using MODIS bands 4 and 7, 1 and 7, 4 and 6 or 1 and 6 perform best. A common threshold for each NDSI across all sites was more appropriate than locally adaptive thresholds. In general, NDSIs that use band 7 have a negligible increase in Commission Error over those that use band 6 but are more sensitive to water presence in mixed land cover conditions typical of moderate spatial resolution analyses. The best performing NDSI is comparable to the combined index but with less variability in performance across sites, suggesting a more succinct and robust flood detection method. PMID:24586381

  5. Comparative Analysis of Normalised Difference Spectral Indices Derived from MODIS for Detecting Surface Water in Flooded Rice Cropping Systems

    PubMed Central

    Boschetti, Mirco; Nutini, Francesco; Manfron, Giacinto; Brivio, Pietro Alessandro; Nelson, Andrew

    2014-01-01

    Identifying managed flooding in paddy fields is commonly used in remote sensing to detect rice. Such flooding, followed by rapid vegetation growth, is a reliable indicator to discriminate rice. Spectral indices (SIs) are often used to perform this task. However, little work has been done on determining which spectral combination in the form of Normalised Difference Spectral Indices (NDSIs) is most appropriate for surface water detection or which thresholds are most robust to separate water from other surfaces in operational contexts. To address this, we conducted analyses on satellite and field spectral data from an agronomic experiment as well as on real farming situations with different soil and plant conditions. Firstly, we review and select NDSIs proposed in the literature, including a new combination of visible and shortwave infrared bands. Secondly, we analyse spectroradiometric field data and satellite data to evaluate mixed pixel effects. Thirdly, we analyse MODIS data and Landsat data at four sites in Europe and Asia to assess NDSI performance in real-world conditions. Finally, we test the performance of the NDSIs on MODIS temporal profiles in the four sites. We also compared the NDSIs against a combined index previously used for agronomic flood detection. Analyses suggest that NDSIs using MODIS bands 4 and 7, 1 and 7, 4 and 6 or 1 and 6 perform best. A common threshold for each NDSI across all sites was more appropriate than locally adaptive thresholds. In general, NDSIs that use band 7 have a negligible increase in Commission Error over those that use band 6 but are more sensitive to water presence in mixed land cover conditions typical of moderate spatial resolution analyses. The best performing NDSI is comparable to the combined index but with less variability in performance across sites, suggesting a more succinct and robust flood detection method. PMID:24586381

  6. An Emerging Role of Degrading Proteinases in Hypertension and the Metabolic Syndrome: Autodigestion and Receptor Cleavage

    PubMed Central

    2011-01-01

    One of the major challenges for hypertension research is to identify the mechanisms that cause the comorbidities encountered in many hypertensive patients, as seen in the metabolic syndrome. An emerging body of evidence suggests that human and experimental hypertensives may exhibit uncontrolled activity of proteinases, including the family of matrix metalloproteinases, recognized for their ability to restructure the extracellular matrix proteins and to play a role in hypertrophy. We propose a new hypothesis that provides a molecular framework for the comorbidities of hypertension, diabetes, capillary rarefaction, immune suppression, and other cell and organ dysfunctions due to early and uncontrolled extracellular receptor cleavage by active proteinases. The proteinase and signaling activity in hypertensives requires further detailed analysis of the proteinase expression, the mechanisms causing proenzyme activation, and identification of the proteinase substrate. This work may open the opportunity for reassessment of old interventions and development of new interventions to manage hypertension and its comorbidities. PMID:22081429

  7. Efficacy and acceptability of perindopril in essential hypertension.

    PubMed

    Sukonthasarn, A; Ratanaprakarn, R; Koanantakul, B; Ngam-Ukos, P

    1994-06-01

    The clinical efficacy and acceptability of once-daily perindopril (4 to 8 mg) monotherapy and in combination with hydrochlorothiazide (50 mg/day) was studied in mild to moderate stable essential hypertensive patients in 4 centres in Thailand. After 2-4 weeks of placebo run-in period, patients received active treatment for 3 months starting with 4 mg perindopril once daily. Dose titration was at second and third month of active treatment if the supine DBP was > 90 mmHg. The dose was doubled and if necessary, 50 mg/day hydrochlorothiazide was added in the last month. The results in 95 patients showed that the mean reduction in supine SBP/DBP at 1, 2 and 3 months of treatment was 10.3/8.0, 13.2/8.7 and 19.1/13.7 mmHg respectively. At the end of the study, 80 per cent of the patients showed normalisation of the supine diastolic blood pressure (supine DBP < or = 90 mmHg) with 30 per cent receiving combined therapy of perindopril and hydrochlorothiazide. There was no significant change in routine haematology or serum biochemistry except for slight increase of potassium levels in patients receiving 8 mg perindopril monotherapy. The incidence of side effects and withdrawal from treatment were quite low. Cough was the major side effect reported comprising 13.6 per cent with only 1 case withdrawn. The study confirms the previous studies that perindopril had satisfactory antihypertensive efficacy and acceptability profiles. PMID:7869013

  8. Pheochromocytoma induced hypertension.

    PubMed

    Andrews, Deborah

    2010-12-01

    Pheochromocytoma (Pheo) is a rare tumor that develops in the core of a chromaffin cell. This article will focus on pheochromocytoma and its affect on the heart. Because the signs and symptoms of a pheochromocytoma are those of the sympathetic nervous system, this tumor is hard to detect and might not be considered early on. In addition, there are many common deferential diagnoses that may lead to a delay of the correct diagnosis of a pheochromocytoma. Uncontrollable hypertension is one of the primary effects of pheochromocytoma. A severe increase in blood pressure (hypertensive crisis) may occur and this can be a life threatening condition that leads to stroke or arrhythmias. African-Americans are disproportionately affected by hypertension and they often go undiagnosed because of a lack of resources or access to care. This tumor is difficult to detect and its effects often mimic many other diagnoses, which often leads to this tumor being a late consideration. The long-term effects of a pheochromocytoma can lead to damage to the heart muscle, congestive heart failure (CHF), increased risk of diabetes, and even death. Nurses need to be aware of the key signs and symptoms of a pheochromocytoma, and to know when testing for this tumor what symptoms should be considered. Patients who suffer from a diagnosis of this tumor need a lot of emotional support and they must follow a strict diet and medication regimen. Nurses can play a vital role in raising awareness in our community about this tumor as well as being a patient advocate. PMID:21516925

  9. Intracranial Hypertension in Children without Papilledema.

    PubMed

    Chelse, Ana B; Epstein, Leon G

    2015-08-01

    Researchers at Nationwide Children's Hospital studied the frequency of intracranial hypertension without papilledema in children followed in a multispecialty pediatric intracranial hypertension clinic. PMID:26933598

  10. [Chronotherapy in arterial hypertension].

    PubMed

    Bendersky, M

    2015-01-01

    The blood pressure profile in most normo- and hypertensive subjects are currently known, as well as the impact their changes induced on the cardio- and cerebrovascular risk. Ambulatory blood pressure monitoring (ABPM) has contributed greatly to the knowledge of this parameter. It to correct the schedule of drug administration (chronotherapy) with changes in any component of the BP profile that have better correlation with risk. These include the nocturnal decrease and the morning BP surge. Investigations in this direction are still scarce, and multicenter studies need to be conducted that can answer the true preventive impact of such modifications. PMID:26180036

  11. Microglia participate in neurogenic regulation of hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure. PMID:26056339

  12. Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

    EPA Science Inventory

    Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

  13. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  14. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  15. Endocrine hypertension – Cushing's syndrome

    PubMed Central

    Singh, Yashpal; Kotwal, Narendra; Menon, A. S.

    2011-01-01

    Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This review discusses the etiology and pathophysiology of hypertension in Cushing's syndrome, while suggesting methods of management of this condition. It also provides an overview of diagnosis and management strategies in this disease. PMID:22145133

  16. Genes influencing circadian differences in blood pressure in hypertensive mice.

    PubMed

    Marques, Francine Z; Campain, Anna E; Davern, Pamela J; Yang, Yee Hwa J; Head, Geoffrey A; Morris, Brian J

    2011-01-01

    Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the 'peak' (n = 12) and 'trough' (n = 6) of diurnal BP. Using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between 'peak' and 'trough' BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension. PMID:21541337

  17. Inflammatory cytokines in pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary hypertension is an “umbrella term” used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension. This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension. PMID:24739042

  18. Hypertension in children and adolescents.

    PubMed

    Mitsnefes, Mark M

    2006-06-01

    Hypertension is one of the most common health problems in the United States and a powerful independent risk factor for cardiovascular and renal disease. Until recently, the incidence of persistent hypertension in children has been low, with a range of 1% to 3%. Recent data indicate that over the last decade, however, average blood pressure levels have risen substantially among American children. Obesity and other lifestyle factors, such as physical inactivity and increased intake of high-calorie, high-salt foods, are thought to be responsible for this trend. Hypertension in children is currently recognized as an important health issue. There is increasing evidence that hypertension has its antecedents during childhood, because adult blood pressure often correlates with childhood blood pressure. Hypertension in children also is viewed as a significant risk factor for the development of cardiovascular disease in adulthood. PMID:16716793

  19. Homocysteine and essential hypertension.

    PubMed

    Rodrigo, Ramón; Passalacqua, Walter; Araya, Julia; Orellana, Myriam; Rivera, Gonzalo

    2003-12-01

    The authors examine the available clinical and experimental data supporting the view that homocysteine, an alternative risk factor of cardiovascular disease, may play a role in the pathogenesis of essential hypertension. The mechanism of this disease has not been elucidated, but it may be related to impairment of vascular endothelial and smooth muscle cell function. Therefore, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Elevated homocysteinemia diminishes the vasodilation by nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. Thus, homocysteine contributes to elevate the blood pressure. Also it is known that elevated plasma levels of homocysteine could lead to oxidant injury to the endothelium. The correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid, could be a useful adjuvant therapy of hypertension. However, further controlled randomized trials are necessary to establish the efficacy and tolerability of these potentially therapeutic agents. PMID:14615465

  20. Midkine in nephrogenesis, hypertension and kidney diseases

    PubMed Central

    Sato, Waichi; Sato, Yuka

    2014-01-01

    Midkine (MK; K; gene abbreviation, Mdk: mus musculus, MDK: homo sapiens) is a multifunctional heparin-binding growth factor that regulates cell growth, survival and migration as well as anti-apoptotic activity in nephrogenesis and development. Proximal tubular epithelial cells are the main sites of MK expression in the kidneys. The pathophysiological roles of MK are diverse, ranging from the development of acute kidney injury (AKI) to the progression of chronic kidney disease, often accompanied by hypertension, renal ischaemia and diabetic nephropathy. The obvious hypertension that develops in Mdk+/+ mouse models of renal ablation compared with Mdk−/− mice eventually leads to progressive renal failure, such as glomerular sclerosis and tubulointerstitial damage associated with elevated plasma angiotensin (Ang) II levels. MK is also induced in the lung endothelium by oxidative stress and subsequently up-regulated by ACE, which hydrolyzes Ang II to induce further oxidative stress, thus accelerating MK generation; this leads to a vicious cycle of positive feedback in the MK-Ang II pathway. Kidney–lung interactions involving positive feedback between the renin-angiotensin system and MK might partly account for the pathogenesis of hypertension and kidney damage. MK is also involved in the pathogenesis of AKI and diabetic nephropathy through the recruitment of inflammatory cells. In contrast, MK plays a protective role against crescentic glomerulonephritis, by down-regulating plasminogen activator inhibitor-1. These diverse actions of MK might open up new avenues for targeted approaches to treating hypertension and various renal diseases. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24106831

  1. Using computer decision support systems in NHS emergency and urgent care: ethnographic study using normalisation process theory

    PubMed Central

    2013-01-01

    Background Information and communication technologies (ICTs) are often proposed as ‘technological fixes’ for problems facing healthcare. They promise to deliver services more quickly and cheaply. Yet research on the implementation of ICTs reveals a litany of delays, compromises and failures. Case studies have established that these technologies are difficult to embed in everyday healthcare. Methods We undertook an ethnographic comparative analysis of a single computer decision support system in three different settings to understand the implementation and everyday use of this technology which is designed to deal with calls to emergency and urgent care services. We examined the deployment of this technology in an established 999 ambulance call-handling service, a new single point of access for urgent care and an established general practice out-of-hours service. We used Normalization Process Theory as a framework to enable systematic cross-case analysis. Results Our data comprise nearly 500 hours of observation, interviews with 64 call-handlers, and stakeholders and documents about the technology and settings. The technology has been implemented and is used distinctively in each setting reflecting important differences between work and contexts. Using Normalisation Process Theory we show how the work (collective action) of implementing the system and maintaining its routine use was enabled by a range of actors who established coherence for the technology, secured buy-in (cognitive participation) and engaged in on-going appraisal and adjustment (reflexive monitoring). Conclusions Huge effort was expended and continues to be required to implement and keep this technology in use. This innovation must be understood both as a computer technology and as a set of practices related to that technology, kept in place by a network of actors in particular contexts. While technologies can be ‘made to work’ in different settings, successful implementation has been

  2. Weight control in the management of hypertension. World Hypertension League.

    PubMed Central

    1989-01-01

    This article, which includes a brief description of the mechanisms and some epidemiological findings in obesity and high blood pressure, sums up present knowledge on a complex subject and provides guidance to medical practitioners on the management of obese hypertensive patients. Weight reduction, together with drug therapy in severe and moderate hypertension, and other non-pharmacological methods and continuing observation in mild hypertension are the essential measures to be applied. In addition to the lowering of blood pressure, weight loss offers several other metabolic and haemodynamic benefits. PMID:2670295

  3. Hypertension in Patients with Cancer

    PubMed Central

    de Souza, Vinicius Barbosa; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade

    2015-01-01

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality. PMID:25742420

  4. Dermatoglyphics in hypertension: a review.

    PubMed

    Wijerathne, Buddhika T B; Meier, Robert J; Agampodi, Thilini C; Agampodi, Suneth B

    2015-01-01

    Hypertension is a major contributor to the global burden of disease and mortality. A major medical advancement would be a better means to ascertain which persons are at higher risk for becoming hypertensive beforehand. To that end, there have been a number of studies showing that certain dermatoglyphic markers are associated with hypertension. This association could be explained if the risk toward developing hypertension later on in life is somehow connected with fetal development of dermatoglyphics. It would be highly valuable from a clinical standpoint if this conjecture could be substantiated since dermatoglyphic markers could then be used for screening out individuals who might be at an elevated risk of becoming hypertensive. The aim of this review was to search for and appraise available studies that pertain to the association between hypertension and dermatoglyphics.A systematic literature search conducted using articles from MEDLINE (PubMed), Trip, Cochran, Google scholar, and gray literature until December 2014. Of the 37 relevant publications, 17 were included in the review. The review performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.This review showed a fairly consistent finding of an increased frequency of whorl patterns along with a higher mean total ridge count in digital dermatoglyphic results in hypertensive samples compared to controls. However, it was imperative to discuss several limitations found in the studies that could make this association as yet unsettled. PMID:26265377

  5. Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors.

    PubMed

    Hay, Meredith

    2016-01-01

    Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension. PMID:26621877

  6. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  7. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  8. In the clinic: hypertension.

    PubMed

    Weir, Matthew R

    2014-12-01

    This issue provides a clinical overview of Hypertension focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. PMID:25437425

  9. Treatment of pulmonary hypertension

    PubMed Central

    Patel, Rajendrakumar; Aronow, Wilbert S.; Patel, Laxeshkumar; Gandhi, Kaushang; Desai, Harit; Kaul, Dhiraj; Sahgal, Sumir P.

    2012-01-01

    Summary Pulmonary arterial hypertension (PAH) is a chronic progressive disease of the pulmonary vasculature characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. PAH is considered a life-threatening condition unless treated. This article provides a comprehensive review of controlled and uncontrolled trials to define the risk-benefit for different therapeutic options of this clinical disorder. Relevant published articles were identified through searches of the National Center for Biotechnology PubMed database. All therapeutic measures for PAH were discussed. Six drugs have been approved in the United States for the treatment of PAH. Extensive medical advancement has been achieved in treatment of PAH. However, none of the approved therapies have shown ability to cure the disease. New research should be performed to develop promising new therapies. PMID:22460104

  10. A complex network analysis of hypertension-related genes

    NASA Astrophysics Data System (ADS)

    Wang, Huan; Xu, Chuan-Yun; Hu, Jing-Bo; Cao, Ke-Fei

    2014-01-01

    In this paper, a network of hypertension-related genes is constructed by analyzing the correlations of gene expression data among the Dahl salt-sensitive rat and two consomic rat strains. The numerical calculations show that this sparse and assortative network has small-world and scale-free properties. Further, 16 key hub genes (Col4a1, Lcn2, Cdk4, etc.) are determined by introducing an integrated centrality and have been confirmed by biological/medical research to play important roles in hypertension.

  11. Sick But Unaware: Hypertension in Indonesia.

    PubMed

    Sohn, Kitae

    2015-01-01

    Discrepancies between self-reported and measured hypertension pose a great risk to health because they prevent timely treatment. Analyzing the Indonesian Family Life Survey, we compared self-reported and measured hypertension to assess the extent of the misclassification of hypertension. Building on this, we estimated factors related to self-reported and measured hypertension. Our results show that different factors were involved in each case, suggesting that they are two different phenomena. More importantly, we estimated factors that increased awareness of hypertension and found that visiting a health facility was a very effective way of increasing awareness of hypertension among hypertensive patients. PMID:26652684

  12. Hyperuricemia, Cardiovascular Disease, and Hypertension

    PubMed Central

    Kuwabara, Masanari

    2016-01-01

    In recent years, there has been an increase in the prevalence of hyperuricemia, and the latter has attracted attention as an adult lifestyle-associated disease, together with hypertension, diabetes, and dyslipidemia. Although hyperuricemia is known to be an independent risk factor for hypertension, whether it is an independent risk factor for cardiovascular disease remains controversial. Recently, some small-scale interventional studies on antihyperuricemic medications showed that the latter improved angina symptoms and prevented cardiovascular disease. Here, we will mainly explain the cause of hyperuricemia and the associations between hyperuricemia, hypertension, and cardiovascular disease based on the latest published evidence. PMID:27195245

  13. Collateral Pathways in Portal Hypertension

    PubMed Central

    Sharma, Malay; Rameshbabu, Chittapuram S.

    2012-01-01

    Presence of portosystemic collateral veins (PSCV) is common in portal hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses exist which exhibit hepatofugal flow. With the development of portal hypertension, transmission of backpressure leads to increased flow in these patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction collateral circulation develops in a hepatopetal direction and portoportal pathways are frequently found. The objective of this review is to illustrate the various PSCV and portoportal collateral vein pathways pertinent to portal hypertension in liver cirrhosis and EHPVO. PMID:25755456

  14. Precursors of Hypertension: A Review

    PubMed Central

    Thomas, John; Neser, William B.; Thomas, Johniene; Semenya, Kofi; Green, Donald R.

    1983-01-01

    Recent advances in hypertension therapy have been remarkable; however, much less is known about those precursors that facilitate preventive and early intervention measures. This review of the literature indicates that relevant precursors are early elevated casual systolic blood pressures, positive family history, and obesity in females. Additional predisposing or enhancing factors point to high sodium ingestion, heavy smoking, and high socioecologic stress. Evidence for a high-risk hypertensive personality is not conclusive. There is a paucity of longitudinal data on hypertension in the black population. PMID:6864814

  15. Effect of 2 different anesthesia methods on stress response in neurosurgical patients with hypertension or normal

    PubMed Central

    Chen, Ying; Jiang, Shan; Wu, Yong

    2016-01-01

    Abstract Hypertensive patients in neurosurgery are becoming more common, which increased the risk of surgical stress response. Meanwhile, the relationship between hypertension and anesthesia methods is unclear on the stress response. The purpose of this study is to compare the effect of different anesthesia methods on high-sensitivity C-reactive protein (Hs-CRP), blood glucose, and leucocyte levels in neurosurgical patients with hypertension or normal. Eighty neurosurgical patients were randomly divided into 4 groups (n = 20): balanced anesthesia group (A), balanced anesthesia with hypertension group (B), total intravenous anesthesia group (C), total intravenous anesthesia with hypertension group (D). The levels of Hs-CRP, blood glucose, leucocyte count, and neutrophil percentage and were detected at before anesthesia (T0), during anesthesia (T1), 2 hours post anesthesia (T2), 24 hours post anesthesia (T3). Patients with hypertension had higher Hs-CRP expression, blood glucose, and neutrophil percentage at time T0 than those of normal, but not leucocyte count. At time T3, patients with hypertension in D group had lower Hs-CRP expression than those in B group (P < 0.01). Patients with normal in C group had lower Hs-CRP expression (P < 0.01), blood glucose (P < 0.05), and leukocyte count (P < 0.05) than those in A group. Both hypertension history and anesthesia method had significant effects on the Hs-CRP expression, blood glucose, and leukocyte count. Total intravenous anesthesia decreases Hs-CRP expressions more efficiently than balanced anesthesia in neurosurgical patients with hypertension or normal. Moreover, total intravenous anesthesia can availably reduce the perioperative stress response by attenuating the increase of blood glucose and leukocyte count in normal tensive patients. PMID:27583931

  16. Role of Musclin in the Pathogenesis of Hypertension in Rat

    PubMed Central

    Li, Ying-Xiao; Cheng, Kai-Chun; Asakawa, Akihiro; Kato, Ikuo; Sato, Yuki; Amitani, Haruka; Kawamura, Namiko; Cheng, Juei-Tang; Inui, Akio

    2013-01-01

    Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. Musclin possesses a region homologous to the natriuretic peptide family. Thus, musclin is found to bind with the natriuretic peptide clearance receptors. However, the role of musclin in vascular regulation remains unclear. In this study, we aim to investigate the direct effect of musclin on vascular tone and to analyze its role in hypertension using the spontaneously hypertensive rats (SHR). In aortic strips isolated from SHR, musclin induced contractions in a dose-dependent manner. We found that the musclin-induced vasoconstriction was more marked in SHR than in normal rats (WKY). Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody. Therefore, mediation of the natriuretic peptide receptor in musclin-induced vasoconstriction can be considered. In addition, similar to the natriuretic peptide receptor, expression of the musclin gene in blood vessels was higher in SHR than in WKY. Injection of musclin markedly increased the blood pressure in rats that can be inhibited by anti-musclin antibodies. Musclin-induced vasoconstriction was more pronounced in SHR than in WKY as in its expression. Taken together, these results suggest that musclin is involved in blood pressure regulation. The higher expression of musclin in hypertension indicates that musclin could be used as a new target for the treatment of hypertension in the future. PMID:23940802

  17. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    PubMed

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains. PMID:25300030

  18. Sex differences in primary hypertension

    PubMed Central

    2012-01-01

    Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

  19. Intracranial Hypertension: Medication and Surgery

    MedlinePlus

    ... http://www.ihrfoundation.org/hypertension/info/C172 Surgery Optic Nerve Fenestration When sight is at risk and drug therapy has been unsuccessful, an optic nerve fenestration (also called an optic nerve sheath ...

  20. [Personality characteristics of hypertensive patients].

    PubMed

    Kubej, P; Korán, M

    1989-02-01

    Essential hypertension, as well-known specialists believe, is due both to genetic and external environment factors. Apart from the steadily growing complexity of social life and various important life events, high-risk factors may also be seen in a certain way of behaviour and man's psychophysiological reactivity. Recent literature on this topic informs about some common characteristics found in the behaviour of hypertensive persons, for example: anxiety in social contacts, suppressed hostility, manifestations of perfectionism, suppression of emotions, exaggerated behavioral adaptability and defensive attitudes to stress stimuli. In accordance with literary data, the control group of hypertensive patients (N = 89) gave evidence of some identical characteristics. Their knowledge permits to carry out more specific attempts at influencing hypertension in a non-pharmacological way. PMID:2720750

  1. Controversies Among the Hypertension Guidelines.

    PubMed

    Ripley, Toni L; Baumert, Mary

    2016-02-01

    Hypertension affects 80 million people in the United States. It remains poorly controlled, with only 54% of diagnosed patients treated to blood pressure targets. Hypertension management is complex in part due to the volume of antihypertensive agents, variable patient needs and responses, and inconsistent design and outcomes from clinical trials. Therefore, trustworthy clinical practice guidelines have a key role in hypertension management. The United States experienced a 10-year gap in publication of hypertension guidelines, followed by multiple guideline publications in 2013. These guidelines led to more controversy than clarity, as there was discordance among them. This review summarizes the guidelines and clinical statements influencing the current debate in order to facilitate appropriate application. PMID:26668216

  2. A case of hypertensive urgency.

    PubMed

    Baum, Laurence

    2016-08-01

    A 41-year-old male Nepalese soldier presented to the primary care medical centre with a 1-week history of fatigue and muscle aches following a trip to Nepal. His BP was 164/98 but was otherwise normal. Four days later he presented with new symptoms of sweating and palpitations and a BP of 200/127 whereupon he was admitted to hospital with the diagnosis of hypertensive crisis. Appropriate investigation and initial management were undertaken, and he was discharged after 12 h on antihypertensive treatment. This case highlights the risk of hypertensive crisis in both diagnosed and silent hypertensive disease, and the review highlights the presentations, initial investigation and different management of hypertensive crisis. PMID:26002343

  3. Systemic hypertension and its management.

    PubMed

    Henik, R A

    1997-11-01

    The pathophysiology of hypertension in dogs and cats, the methods available to monitor blood pressure, and the signs and treatment of hypertension are reviewed. Clinical signs of hypertension are usually referable to target organ damage, most notably in ophthalmic, renal, and cardiovascular tissues, which have a rich arteriolar supply. Blood pressure should be measured in any animal with renal disease, hyperthyroidism, hyperadrenocorticism, retinal detachment or hemorrhage, hyphema, or echocardiographically determined cardiac hypertrophy. All cats with acquired cardiac murmur should also be evaluated for hypertension. Antihypertensive medication should be administered if the indirect blood pressure in cats is consistently over 170/100 mmHg, or if the indirect blood pressure in dogs is greater than 180/100 mmHg. PMID:9348634

  4. [Resistant hypertension : What is it?].

    PubMed

    Luft, F C

    2015-03-01

    When blood pressure is poorly controlled despite treatment with a diuretic and two antihypertensive drugs at adequate doses, the hypertension is termed resistant. The prevalence of resistant hypertension is increasing. Once pseudo-resistance due to poor compliance, secondary forms of hypertension, and massive salt consumption have been excluded, some authorities maintain that blood pressure can be invariably lowered using minoxidil or mineralocorticoid receptor blockade. I also adhered to this belief until we encountered a patient who despite treatment with seven antihypertensive agents, electrical carotid sinus stimulation, and catheter-based renal denervation continued to exhibit extraordinarily high blood pressure values. I am now convinced that resistant hypertension does indeed exist. The prevalence of such patients can be substantially reduced by means of a thorough history and physical examination, determining drug serum concentrations, and excluding secondary causes. PMID:25668441

  5. PDE3A mutations cause autosomal dominant hypertension with brachydactyly.

    PubMed

    Maass, Philipp G; Aydin, Atakan; Luft, Friedrich C; Schächterle, Carolin; Weise, Anja; Stricker, Sigmar; Lindschau, Carsten; Vaegler, Martin; Qadri, Fatimunnisa; Toka, Hakan R; Schulz, Herbert; Krawitz, Peter M; Parkhomchuk, Dmitri; Hecht, Jochen; Hollfinger, Irene; Wefeld-Neuenfeld, Yvette; Bartels-Klein, Eireen; Mühl, Astrid; Kann, Martin; Schuster, Herbert; Chitayat, David; Bialer, Martin G; Wienker, Thomas F; Ott, Jürg; Rittscher, Katharina; Liehr, Thomas; Jordan, Jens; Plessis, Ghislaine; Tank, Jens; Mai, Knut; Naraghi, Ramin; Hodge, Russell; Hopp, Maxwell; Hattenbach, Lars O; Busjahn, Andreas; Rauch, Anita; Vandeput, Fabrice; Gong, Maolian; Rüschendorf, Franz; Hübner, Norbert; Haller, Hermann; Mundlos, Stefan; Bilginturan, Nihat; Movsesian, Matthew A; Klussmann, Enno; Toka, Okan; Bähring, Sylvia

    2015-06-01

    Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor. Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated. In vitro analyses of mesenchymal stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A-mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension. PMID:25961942

  6. A Practical Approach to Hypertension

    PubMed Central

    Dodek, Arthur; Wilkins, Graeme

    1976-01-01

    At least ten percent of the adult population has hypertension. Detection and effective treatment of hypertension are imperative in order to prevent the cardiovascular consequences. Effective antihypertensive treatment reduces morbidity and mortality. Weight reduction and sodium restriction are important fundamentals, and diuretics are the cornerstone of drug therapy. In order to increase patient compliance, treatment should be simple and drugs given twice daily wherever possible. PMID:20469276

  7. Hypertension in the emergency department.

    PubMed

    Jackson, R E

    1988-05-01

    Hypertensive emergencies are now rare and are recognized by the deleterious effect on end-organs. Prompt, efficacious treatment is critical, and the current drug of choice for most episodes is sodium nitroprusside. Hypertensive urgencies are more common than are emergencies, and are distinguished by diastolic pressures greater than 115 mm Hg without end-organ dysfunction. Although there are many efficacious agents, one excellent choice is nifedipine. PMID:3280299

  8. Selection of low-variance expressed Malus x domestica (apple) genes for use as quantitative PCR reference genes (housekeepers)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To accurately measure gene expression using PCR-based approaches, there is the need for reference genes that have low variance in expression (housekeeping genes) to normalise the data for RNA quantity and quality. For non-model species such as Malus x domestica (apples), previously, the selection of...

  9. The hidden epidemic of hypertension.

    PubMed

    Grenfell, Robert; Lee, Rebecca; Stavreski, Bill; Page, Karen

    2014-04-01

    The majority of cardiovascular disease (CVD) is caused by risk factors that can be controlled, treated or modified. In terms of attributable deaths, the leading cardiovascular disease risk factor is hypertension. The Australian Health Survey results showed some startling figures-4.6 million adult Australians are hypertensive (>140/90 mmHg). Further, a fifth of the adult population experience hypertension, with more than two out of three not attaining blood pressure target levels. This is despite an estimated cost of $1 billion per annum spent on managing hypertension. It is now well recognised that the level of risk for coronary heart disease is linked to an individual's risk profile. Results indicate that many Australians have multiple risk factors, including hypertension. It could be considered that these numbers provide a proxy indicator of secondary prevention failure. Considerable attention needs to be given to the assessment of the combined risk of those with hypertension enabling effective management of identified, modifiable risk factors. We look forward to presenting the absolute risk profiles when the Australian Health Survey biometric results are released. PMID:24468162

  10. Genistein attenuates low temperature induced pulmonary hypertension in broiler chicks by modulating endothelial function.

    PubMed

    Yang, Ying; Gao, Mingyu; Wu, Zhenlong; Guo, Yuming

    2010-12-15

    Pulmonary arterial hypertension is characterized by high pulmonary blood pressure, vascular remodeling and right ventricular hypertrophy. In the present study, we investigated whether genistein would prevent the development of low temperature-induced pulmonary hypertension in broilers. Hemodynamic parameters, vascular remodeling, the expression of endothelial nitric oxide and endothelin-1 content in lung tissue were evaluated. The results demonstrated that genistein significantly reduced pulmonary arterial hypertension and suppressed pulmonary arterial vascular remodeling without affecting broilers' performance. The beneficial effects appeared to be mediated by restoring endothelial function especially endothelial nitric oxide and endothelin-1, two critical vasoactive molecules that associated with the development of hypertension. Genistein supplementation might be a potential therapeutic strategy for the treatment of pulmonary hypertension. PMID:20854807

  11. Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

    PubMed Central

    Barth, Emeline; Bouvaist, Hélène; Marlière, Stéphanie; Ninet, Gérard; Vanzetto, Gérald

    2009-01-01

    A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up. PMID:19758423

  12. The moral experience of illness and its impact on normalisation: Examples from narratives with Punjabi women living with rheumatoid arthritis in the UK.

    PubMed

    Sanderson, Tessa; Calnan, Michael; Kumar, Kanta

    2015-11-01

    The moral component of living with illness has been neglected in analyses of long-term illness experiences. This article attempts to fill this gap by exploring the role of the moral experience of illness in mediating the ability of those living with a long-term condition (LTC) to normalise. This is explored through an empirical study of women of Punjabi origin living with rheumatoid arthritis (RA) in the UK. Sixteen informants were recruited through three hospitals in UK cities and interviews conducted and analysed using a grounded theory approach. The intersection between moral experience and normalisation, within the broader context of ethnic, gender and socioeconomic influences, was evident in the following: disruption of a core lived value (the centrality of family duty), beliefs about illness causation affecting informants' 'moral career', and perceived discrimination in the workplace. The data illustrate the importance of considering an ethnic community's specific values and beliefs when understanding differences in adapting to LTCs and changing identities. PMID:26139357

  13. Marriage, mortgage, motherhood: what longitudinal studies can tell us about gender, drug 'careers' and the normalisation of adult 'recreational' drug use.

    PubMed

    Measham, Fiona; Williams, Lisa; Aldridge, Judith

    2011-11-01

    Through a consideration of quantitative and qualitative data obtained from young women aged 18-28 in the later years of the North West England Longitudinal Study, this paper explores how women's drug careers develop, progressing the authors' normalisation thesis of 'recreational' drug use from adolescence into adulthood. Longitudinal studies are here compared with repeated cross-sectional surveys more usually favoured and funded by governments. The authors argue that firstly, in relation to methodology, longitudinal studies provide a unique opportunity to elucidate how drug careers develop across the life course and to chart the various impacts of life events and transitions on these careers and vice versa. Secondly, through this exploration of gender differences in drug careers and life transitions, we develop an age and gender-sensitive understanding of how recreational drug use fits into women's adult lives. The paper concludes that the challenge for policy makers is how to address adult women's 'normalised' recreational drug use, in the face of a regime focused on educational provision aimed at adolescent prevention; public health information designed for teenagers; and treatment resources focused on predominantly male and non parenting problem drug users, and the links between addiction and acquisitive crime. PMID:21782407

  14. Matrix-normalised quantification of species by threshold-calibrated competitive real-time PCR: allergenic peanut in food as one example.

    PubMed

    Holzhauser, Thomas; Kleiner, Kornelia; Janise, Annabella; Röder, Martin

    2014-11-15

    A novel method to quantify species or DNA on the basis of a competitive quantitative real-time polymerase chain reaction (cqPCR) was developed. Potentially allergenic peanut in food served as one example. Based on an internal competitive DNA sequence for normalisation of DNA extraction and amplification, the cqPCR was threshold-calibrated against 100mg/kg incurred peanut in milk chocolate. No external standards were necessary. The competitive molecule successfully served as calibrator for quantification, matrix normalisation, and inhibition control. Although designed for verification of a virtual threshold of 100mg/kg, the method allowed quantification of 10-1,000 mg/kg peanut incurred in various food matrices and without further matrix adaption: On the basis of four PCR replicates per sample, mean recovery of 10-1,000 mg/kg peanut in chocolate, vanilla ice cream, cookie dough, cookie, and muesli was 87% (range: 39-147%) in comparison to 199% (range: 114-237%) by three commercial ELISA kits. PMID:24912697

  15. [Postpartum pulmonary hypertension].

    PubMed

    Escalante, Juan Pablo; Diez, Ana; Figueroa Casas, Marcelo; Lasave, Alejandro; Cursack, Guillermo; Poy, Carlos; Rodríguez, María Soledad; Galuppo, Marcela; Zapata, Gerardo

    2015-01-01

    Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery. PMID:25637900

  16. Developmental programming and hypertension

    PubMed Central

    Nuyt, Anne Monique; Alexander, Barbara T.

    2009-01-01

    Purpose of review There is a growing body of evidence linking adverse events or exposures during early life and adult-onset diseases. After important epidemiological studies from many parts of the world, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements of adverse perinatal conditions, such as nutrition, oxidants, and toxins exposures. This review will focus on advances in our comprehension of developmental programming of hypertension. Recent findings Recent studies have unraveled important mechanisms of oligonephronia and impaired renal function, altered vascular function and structure as well as sympathetic regulation of the cardiovascular system. Furthermore, interactions between prenatal insults and postnatal conditions are the subject of intensive research. Prematurity vs. intrauterine growth restriction modulate differently programming of high blood pressure. Along with antenatal exposure to glucocorticoids and imbalanced nutrition, a critical role for perinatal oxidative stress is emerging. Summary While the complexity of the interactions between antenatal and postnatal influences on adult blood pressure is increasingly recognized, the importance of postnatal life in (positively) modulating developmental programming offers the hope of a critical window of opportunity to reverse programming and prevent or reduce related adult-onset diseases. PMID:19434052

  17. New therapies for arterial hypertension.

    PubMed

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures. PMID:26730462

  18. CaMK4 Gene Deletion Induces Hypertension

    PubMed Central

    Santulli, Gaetano; Cipolletta, Ersilia; Sorriento, Daniela; Del Giudice, Carmine; Anastasio, Antonio; Monaco, Sara; Maione, Angela Serena; Condorelli, Gianluigi; Puca, Annibale; Trimarco, Bruno; Illario, Maddalena; Iaccarino, Guido

    2012-01-01

    Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4−/− mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.) PMID:23130158

  19. Comprehensive management of hypertensive emergencies and urgencies.

    PubMed

    Mansoor, George A; Frishman, William H

    2002-01-01

    Despite advances in chronic hypertension management, hypertensive emergencies and urgencies remain as serious complications. Much of this relates to poor compliance with effective antihypertensive management. Hypertensive emergencies and urgencies can also be seen as the initial manifestations of hypertension in pregnancy and in the perioperative period. Multiple classes of intravenous antihypertensive drugs are available to treat hypertensive emergencies, and specific agents may have an advantage in a given clinical situation. Orally active agents are used to treat hypertensive urgencies, and include clonidine, angiotensin-converting enzyme inhibitors, and labetalol. Most patients respond to drug therapy, but problems may arise related to a rapid normalization of blood pressure. PMID:12441013

  20. Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.

    PubMed

    Watanabe, Takuya; Arita, Shigeko; Shiraishi, Yuji; Suguro, Toshiaki; Sakai, Tetsuo; Hongo, Shigeki; Miyazaki, Akira

    2009-01-01

    Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases

  1. PPARs Link Early Life Nutritional Insults to Later Programmed Hypertension and Metabolic Syndrome

    PubMed Central

    Tain, You-Lin; Hsu, Chien-Ning; Chan, Julie Y. H.

    2015-01-01

    Hypertension is an important component of metabolic syndrome. Adulthood hypertension and metabolic syndrome can be programmed in response to nutritional insults in early life. Peroxisome proliferator-activated receptors (PPARs) serve as a nutrient-sensing signaling linking nutritional programming to hypertension and metabolic syndrome. All three members of PPARs, PPARα, PPARβ/δ, and PPARγ, are expressed in the kidney and involved in blood pressure control. This review provides an overview of potential clinical applications of targeting on the PPARs in the kidney to prevent programmed hypertension and metabolic syndrome, with an emphasis on the following areas: mechanistic insights to interpret programmed hypertension; the link between the PPARs, nutritional insults, and programmed hypertension and metabolic syndrome; the impact of PPAR signaling pathway in a maternal high-fructose model; and current experimental studies on early intervention by PPAR modulators to prevent programmed hypertension and metabolic syndrome. Animal studies employing a reprogramming strategy via targeting PPARs to prevent hypertension have demonstrated interesting results. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies, to halt the globally-growing epidemic of metabolic syndrome-related diseases. PMID:26712739

  2. Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension.

    PubMed

    Leibovitch, Leah; Matok, Ilan; Paret, Gideon

    2007-01-01

    Pulmonary hypertension is characterised by a progressive increase in pulmonary vascular resistance and a poor prognosis. The exact underlying mechanisms are still poorly understood; however, it is hypothesised that pulmonary medial hypertrophy and endothelial dysfunction lead to impaired production of vasodilators such as nitric oxide (NO) and prostacyclin, and increased expression of vasoconstrictors such as endothelin-1. The current treatment modalities for pulmonary hypertension include conventional supportive therapies and more specific pharmacological therapies that are targeted at abnormalities of endothelial function. NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Sildenafil citrate is a highly selective inhibitor of PDE5. Investigations in animal models and recent clinical case reports with some studies in the paediatric population suggest that sildenafil may be a promising agent in treating pulmonary hypertension. The effect of sildenafil on pulmonary vasculature appears to be independent of the underlying cause, thereby providing a role in idiopathic pulmonary arterial hypertension (PAH), PAH associated with congenital heart disease, pulmonary hypertension secondary to lung disease or persistent pulmonary hypertension of the newborn. It may also be beneficial in postoperative pulmonary hypertension and in neonates who are difficult to wean from inhaled NO. It is easily administered and effective, and has minimal systemic adverse effects. Although the reported results in children with pulmonary hypertension are promising, it is an experimental drug and large-scale randomised controlled studies are required to validate the safety, efficacy and dosage in the paediatric population. PMID:17209664

  3. Hyperthyroidism and pulmonary hypertension.

    PubMed

    Marvisi, M; Brianti, M; Marani, G; Del Borello, R; Bortesi, M L; Guariglia, A

    2002-04-01

    In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2. The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH. PMID:11999999

  4. Salt intake and hypertension therapy.

    PubMed

    Milan, Alberto; Mulatero, Paolo; Rabbia, Franco; Veglio, Franco

    2002-01-01

    Hypertension is a risk factor for cardiovascular and renal organ damage. Environmental conditions affect the development of high blood pressure (BP), although genetic influences are also important. Current international guidelines recommend reducing dietary sodium to no more than 100 mmol (about 2.4 g sodium or approximately 6 g salt) per day to prevent BP rising; the current intake of sodium in industrialized countries is approximately double the recommended amount. Clinical trials (DASH and TOHP studies) have shown that dietary factors are fundamental in the prevention and control of BP. Low dietary sodium intake is particularly effective in preventing hypertension in subjects with an increased risk such as the overweight, borderline hypertensives or the elderly. A low-salt diet combined with anti-hypertensive therapies facilitates BP reduction independent of race. The hypotensive effect of calcium channel blockers is less dependent on salt intake than other drugs, such as ACE inhibitors or diuretics. Reduced sodium intake associated with other dietary changes (such as weight loss, and increasing potassium, calcium and magnesium intake) are important instruments for the prevention and therapy of hypertension. PMID:11936420

  5. Pathophysiological Links Among Hypertension and Alzheimer's Disease.

    PubMed

    Carnevale, Daniela; Perrotta, Marialuisa; Lembo, Giuseppe; Trimarco, Bruno

    2016-03-01

    Genetic Alzheimer's disease (AD) accounts for only few AD cases and is almost exclusively associated to increased amyloid production in the brain. Instead, the majority of patients is affected with the AD sporadic form with typical alterations of clearance mechanisms of the brain. Most studies use engineered animal models that mimic genetic AD. Since it is emerging the existence of a pathophysiological link between cardiovascular risk factors and AD etiology, the strategy to develop animal models of vascular related AD pathology could be the key toward developing novel successful therapies. On this issue, we have demonstrated that mice that have been chronically subjected to high blood pressure show deposition of amyloid aggregates, the main histological feature of AD, and loss of memory in specific tasks. More importantly, we have identified that the hypertensive challenge increases the expression of the receptor for advanced glycated end products (RAGE), leading to beta-amyloid (Aβ) deposition and learning impairment. Here, we review different murine models of hypertension, induced either pharmacologically or mechanically, leading in the long time to plaque formation in the brain parenchyma and around blood vessels. The major findings obtained till now in this particular experimental setting allow us to suggest that this appears to be a unique possibility to study the pathogenetic mechanisms of sporadic AD triggered by vascular risk factors. PMID:26054481

  6. Renal P2 receptors and hypertension.

    PubMed

    Menzies, R I; Unwin, R J; Bailey, M A

    2015-01-01

    The regulation of extracellular fluid volume is a key component of blood pressure homeostasis. Long-term blood pressure is stabilized by the acute pressure natriuresis response by which changes in renal perfusion pressure evoke corresponding changes in renal sodium excretion. A wealth of experimental evidence suggests that a defect in the pressure natriuresis response contributes to the development and maintenance of hypertension. The mechanisms underlying the relationship between renal perfusion pressure and sodium excretion are incompletely understood. Increased blood flow through the vasa recta increases renal interstitial hydrostatic pressure, thereby reducing the driving force for transepithelial sodium reabsorption. Paracrine signalling also contributes to the overall natriuretic response by inhibiting tubular sodium reabsorption in several nephron segments. In this brief review, we discuss the role of purinergic signalling in the renal control of blood pressure. ATP is released from renal tubule and vascular cells in response to increased flow and can activate P2 receptor subtypes expressed in both epithelial and vascular endothelial/smooth muscle cells. In concert, these effects integrate the vascular and tubular responses to increased perfusion pressure and targeting P2 receptors, particularly P2X7, may prove beneficial for treatment of hypertension. PMID:25345692

  7. Congenital ductus arteriosus aneurysm: an unusual cause of transient neonatal hypertension

    PubMed Central

    Murki, Srinivas; Deshbhatla, Sai Kiran; Sharma, Deepak; Rao, Nageshwar; Verma, Sudeep

    2014-01-01

    Case 1: A term male child was re-admitted on day 10 of life due to acute onset of respiratory distress. Physical examination revealed tachypnoea, tachycardia and blood pressure (BP) above the 95th centile in all four limbs. Cardiovascular examination revealed a short systolic murmur on the sternal border. Abdomen showed hepatomegaly of 3 cm below the costal margin. Chest X-ray showed a cardiothoracic ratio of 0.65 with normal vascularity. Ultrasound and Doppler of the kidneys and brain were normal. The high parasternal view showed a large ductus arteriosus aneurysm (DAA) of 2.0×2.5 cm. The baby was managed with inotropes and antihypertensives. CT angiogram showed 1.6×0.6 cm thrombosed DAA, which was extending from the posterior descending aorta to the ampulla. With the resolution of aneurysm BPs normalised and antihypertensives were stopped at 6 weeks of age. Case 2: A premature male neonate weighing 1.2 kg was admitted to the neonatal intensive care unit for respiratory distress syndrome. On the 4th day of life during routine measurement of vitals, the BP was consistently above 95th centile in all four limbs. Blood tests revealed thrombocytopenia that persisted inspite of single donor transfusions. The evaluation for sepsis was negative. The ultrasound and Dopplers of the kidneys and brain were all normal. A transthoracic echocardiogram showed a large DAA measuring 5×1.8 mm. Hypertension was managed with antihypertensives. Serial transthoracic echocardiogram showed organising DAA. CT angiogram showed 6 mm×2 mm thrombosed DAA. As the arterial BP normalised, antihypertensives were stopped on day 15 of life. The baby was discharged on day 29 of life and on follow-up BP remained normal. PMID:24798362

  8. Who Is at Risk for Pulmonary Hypertension?

    MedlinePlus

    ... exact number of people who have pulmonary hypertension (PH) isn't known. Group 1 pulmonary arterial hypertension ( ... have group 1 PAH tend to be overweight . PH that occurs with another disease or condition is ...

  9. Infantile Renovascular Hypertension with Failure to Thrive.

    PubMed

    Phillips, Amanda R; Eliason, Jonathan L; Stanley, James C; Coleman, Dawn M

    2016-05-01

    Severe hypertension in infancy is a rare cause of failure to thrive. The successful surgical management of this disease in an infant having refractory renovascular hypertension and growth failure is reported. PMID:26965798

  10. An Update on Inpatient Hypertension Management.

    PubMed

    Axon, R Neal; Turner, Mason; Buckley, Ryan

    2015-11-01

    Hypertension is highly prevalent affecting nearly one third of the US adult population. Though generally approached as an outpatient disorder, elevated blood pressure is observed in a majority of hospitalized patients. The spectrum of hypertensive disease ranges from patients with hypertensive emergency including markedly elevated blood pressure and associated end-organ damage to asymptomatic patients with minimally elevated pressures of unclear significance. It is important to note that current evidence-based hypertension guidelines do not specifically address inpatient hypertension. This narrative review focuses primarily on best practices for diagnosing and managing nonemergent hypertension in the inpatient setting. We describe examples of common hypertensive syndromes, provide suggestions for optimal post-acute management, and point to evidence-based or consensus guidelines where available. In addition, we describe a practical approach to managing asymptomatic elevated blood pressure observed in the inpatient setting. Finally, arranging effective care transitions to ensure optimal ongoing hypertension management is appropriate in all cases. PMID:26362300

  11. Pressure Points: Preventing and Controlling Hypertension

    MedlinePlus

    ... Issue Past Issues Pressure Points: Preventing and Controlling Hypertension Past Issues / Summer 2006 Table of Contents For ... diagnosed with high blood pressure." Aditional Information On Hypertension MedlinePlus: High blood pressure: http://www.nlm.nih. ...

  12. QT dispersion in adult hypertensives.

    PubMed Central

    Sani, Isa Muhammad; Solomon, Danbauchi Sulei; Imhogene, Oyati Albert; Ahmad, Alhassan Muhammad; Bala, Garko Sani

    2006-01-01

    Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country. PMID:16623077

  13. Schistosomiasis-associated pulmonary hypertension

    PubMed Central

    Mocumbi, Ana Olga H.; Kim, Nick H.; Mandel, Jess

    2014-01-01

    Abstract Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension–like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy. PMID:25610596

  14. Pharmacologic management of childhood hypertension.

    PubMed

    Sinaiko, A R

    1993-02-01

    Antihypertensive drug therapy is used in children primarily to treat secondary forms of hypertension, because the prevalence of essential hypertension in the first decade of life is considerably less than 1% of the childhood population. This prevalence increases during the second decade of life, but the percentage of teenagers with essential hypertension continues to be low. Pharmaceutical companies have been able to target drug development to specific physiologic and biochemical systems. The converting enzyme inhibitors and calcium-channel blockers have greatly improved the success of therapy concomitant with a reduction in the incidence of adverse effects. The result has been a major change during the past decade in the recommendations for antihypertensive drug therapy. PMID:8417406

  15. Implementing a provider-initiated testing and counselling (PITC) intervention in Cape town, South Africa: a process evaluation using the normalisation process model

    PubMed Central

    2013-01-01

    Background Provider-initiated HIV testing and counselling (PITC) increases HIV testing rates in most settings, but its effect on testing rates varies considerably. This paper reports the findings of a process evaluation of a controlled trial of PITC for people with sexually transmitted infections (STI) attending publicly funded clinics in a low-resource setting in South Africa, where the trial results were lower than anticipated compared to the standard Voluntary Counselling and Testing (VCT) approach. Method This longitudinal study used a variety of qualitative methods, including participant observation of project implementation processes, staff focus groups, patient interviews, and observation of clinical practice. Data were content analysed by identifying the main influences shaping the implementation process. The Normalisation Process Model (NPM) was used as a theoretical framework to analyse implementation processes and explain the trial outcomes. Results The new PITC intervention became embedded in practice (normalised) during a two-year period (2006 to 2007). Factors that promoted the normalising include strong senior leadership, implementation support, appropriate accountability mechanisms, an intervention design that was responsive to service needs and congruent with professional practice, positive staff and patient perceptions, and a responsive organisational context. Nevertheless, nurses struggled to deploy the intervention efficiently, mainly because of poor sequencing and integration of HIV and STI tasks, a focus on HIV education, tension with a patient-centred communication style, and inadequate training on dealing with the operational challenges. This resulted in longer consultation times, which may account for the low test coverage outcome. Conclusion Leadership and implementation support, congruent intervention design, and a responsive organisational context strengthened implementation. Poor compatibility with nurse skills on the level of the

  16. Refeeding hypertension in dietary obesity

    SciTech Connect

    Ernsberger, P.; Nelson, D.O. )

    1988-01-01

    A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac {beta}-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of ({sup 3}H)dihydroalpranolol; and (2) the decrease in heart rate as a result of {beta}-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.

  17. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    PubMed Central

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  18. Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study.

    PubMed

    Newhouse, Stephen J; Wallace, Chris; Dobson, Richard; Mein, Charles; Pembroke, Janine; Farrall, Martin; Clayton, David; Brown, Morris; Samani, Nilesh; Dominiczak, Anna; Connell, John M; Webster, John; Lathrop, G Mark; Caulfield, Mark; Munroe, Patricia B

    2005-07-01

    Mutations in the WNK1 gene cause Gordon's syndrome, a rare Mendelian form of hypertension. We assessed whether common WNK1 variants might also contribute to essential hypertension (EH), a multifactorial disorder affecting > 25% of the adult population worldwide. A panel of 19 single nucleotide polymorphisms (SNPs) spanning the gene was selected from public databases and was genotyped in 100 white European families to determine the pattern of linkage disequilibrium, haplotype structure and tagging SNPs for the WNK1 locus. Eight tagging SNPs were identified with 90% power to predict common WNK1 haplotypes and SNPs. Family-based association tests were used to test for association with EH and severity of hypertension in 712 severely hypertensive families from the MRC British Genetics of Hypertension study resource. No association was found between WNK1 polymorphisms or haplotypes with hypertension; however, one SNP rs1468326, located 3 kb from the WNK1 promoter, was found to be nominally associated with severity of hypertension, with both systolic blood pressure (BP) (Z = +2.24, P = 0.025) and diastolic BP (Z = +1.99, P = 0.046). We also found nominal support for association of one common WNK1 haplotype with increased systolic BP (Z = +1.91, P = 0.053). This is the first study to perform haplotype association analysis of the WNK1 gene with EH. This finding of association between a SNP near the promoter region and the severity of hypertension suggests that increased expression of WNK1 might contribute to BP variability and susceptibility to EH similar to the mechanism of hypertension observed in Gordon's syndrome. PMID:15888480

  19. Risk Factors in Adolescent Hypertension.

    PubMed

    Ewald, D Rose; Haldeman PhD, Lauren A

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  20. Risk Factors in Adolescent Hypertension

    PubMed Central

    Ewald, D. Rose; Haldeman, Lauren A.

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  1. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology.

    PubMed

    Humbert, M

    2010-03-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy. PMID:20956167

  2. Hypertension: Strengths and limitations of the JNC 8 hypertension guidelines.

    PubMed

    Mancia, Giuseppe

    2014-04-01

    The Eighth Joint National Committee (JNC 8) guidelines on hypertension have generated great interest among physicians. These guidelines differ from those published in 2003 (the JNC 7) - in the document format, blood-pressure cut-off values, and recommendations for antihypertensive drug use. The JNC 8 have some limitations that could affect clinical practice. PMID:24514021

  3. Renovascular hypertension: Pathophysiology, diagnosis, and treatment

    SciTech Connect

    Glorioso, N.; Laragh, J.H.; Rappelli, A.

    1987-01-01

    This book contains 42 selections. Some of the titles are: Clinical Pharmacology of Two Synthetic Atrial Natriuretics Peptides; Reflex Control of Renin Release in Normotensive and Hypertensive Humans; Renal Blood flow in Renovascular Hypertension; and Radioisotopic Studies in Renovascular Hypertension Before and After Surgery or Percutaneous Transluminal Renal Angioplasty.

  4. The normalised difference vegetation index obtained from agrometeorological standard radiation sensors: A comparison with ground-based multiband spectroradiometer measurements during the phenological development of an oat canopy.

    PubMed

    Wittich, Klaus-Peter; Kraft, Martin

    2008-01-01

    Following the methodology of K. F. Huemmrich and colleagues [Huemmrich et al. (1999) J Geophys Res 104:27,935-27,944], agrometeorological standard radiation sensors, i.e. two photosynthetically active radiation sensors and an albedometer, were used to measure the broadband visible and optical-infrared reflectance of an oat plot during its whole growth period. From these reflectance data - recorded as 15-min averages and pooled to daily means - the seasonal cycle of the normalised difference vegetation index (NDVI) was calculated. In addition, a ground-based multi-channel spectroradiometer was used as a reference to estimate narrowband "green" and "red" NDVIs at weekly intervals near noon. The narrowband "green" NDVI was shown to be consistent with the simultaneous broadband 15-min NDVI. This shows that the configuration of agrometeorological radiation sensors is suitable to adequately track phenological crop dynamics. PMID:17576603

  5. Molecular pathogenesis of pulmonary arterial hypertension

    PubMed Central

    Rabinovitch, Marlene

    2012-01-01

    Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH — together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function — have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways. PMID:23202738

  6. The economic costs of natural disasters globally from 1900-2015: historical and normalised floods, storms, earthquakes, volcanoes, bushfires, drought and other disasters

    NASA Astrophysics Data System (ADS)

    Daniell, James; Wenzel, Friedemann; Schaefer, Andreas

    2016-04-01

    For the first time, a breakdown of natural disaster losses from 1900-2015 based on over 30,000 event economic losses globally is given based on increased analysis within the CATDAT Damaging Natural Disaster databases. Using country-CPI and GDP deflator adjustments, over 7 trillion (2015-adjusted) in losses have occurred; over 40% due to flood/rainfall, 26% due to earthquake, 19% due to storm effects, 12% due to drought, 2% due to wildfire and under 1% due to volcano. Using construction cost indices, higher percentages of flood losses are seen. Depending on how the adjustment of dollars are made to 2015 terms (CPI vs. construction cost indices), between 6.5 and 14.0 trillion USD (2015-adjusted) of natural disaster losses have been seen from 1900-2015 globally. Significant reductions in economic losses have been seen in China and Japan from 1950 onwards. An AAL of around 200 billion in the last 16 years has been seen equating to around 0.25% of Global GDP or around 0.1% of Net Capital Stock per year. Normalised losses have also been calculated to examine the trends in vulnerability through time for economic losses. The normalisation methodology globally using the exposure databases within CATDAT that were undertaken previously in papers for the earthquake and volcano databases, are used for this study. The original event year losses are adjusted directly by capital stock change, very high losses are observed with respect to floods over time (however with improved flood control structures). This shows clear trends in the improvement of building stock towards natural disasters and a decreasing trend in most perils for most countries.

  7. Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension.

    PubMed

    Bakri, Mahinur; Yi, Yang; Chen, Ling-Dan; Aisa, Haji Akber; Wang, Mong-Heng

    2014-04-01

    In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers. PMID:24863351

  8. Brain Injury After Intracerebral Hemorrhage in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Gang; Bao, Xuhui; Xi, Guohua; Keep, Richard; Thompson, B. Gregory; Hua, Ya

    2011-01-01

    Object Hypertension is the main cause of spontaneous intracerebral hemorrhages (ICH), but the effects of hypertension on ICH-induced brain injury have not been well studied. In this study, we examined ICH-induced brain injury in spontaneously hypertensive rats (SHR). Methods This two-part study was performed on 12 weeks old male SHR and Wistar Kyoto (WKY) rats. First, rats received an intracaudate injection of 0.3 units collagenase and hematoma sizes were determined at 24 hours. Second, rats were injected with 100-μL autologous whole blood into the right basal ganglia. Brain edema, neuronal death, ferritin expression, microglia activation, and neurological deficits were examined. Results Hematoma sizes were the same in SHR and WKY rats 24 hours after collagenase injection. SHR had greater neuronal death and neurological deficits after blood injection. ICH also resulted in higher brain ferritin levels and stronger activation of microglia in SHR. However, perihematomal brain edema was same in the SHR and WKY rats. Conclusion Moderate chronic hypertension resulted in more severe ICH-induced neuronal death and neurological deficits, but did not exaggerate hematoma enlargement and perihematomal brain edema in the rat ICH models. PMID:21294617

  9. The emerging role of epigenetics in pulmonary hypertension.

    PubMed

    Gamen, Elisabetta; Seeger, Werner; Pullamsetti, Soni Savai

    2016-09-01

    Epigenetics is usually defined as the study of changes in phenotype and gene expression not related to sequence alterations, but rather the chemical modifications of DNA and of its associated chromatin proteins. These modifications can be acquired de novo, being inherited, and represent the way in which genome and environment interact. Recent evidence points to the involvement of epigenetic changes in the pathogenesis of pulmonary hypertension, as they can partly explain how environmental and lifestyle factors can impose susceptibility to pulmonary hypertension and can explain the phenotypic alteration and maintenance of the disease state.In this article, we review the epigenetic regulatory mechanisms that are mediated by DNA methylation, the post-translational modifications of histone tails and noncoding RNAs in the pathogenesis of pulmonary hypertension. Furthermore, pharmacological interventions aimed at epigenetic regulators/modifiers and their outcomes in different cellular and preclinical rodent models are discussed. Lastly, the remaining challenges and future directions in which to explore epigenetic-based therapies in pulmonary hypertension are discussed. PMID:27492834

  10. [PREDICTORS OF RESISTANT ARTERIAL HYPERTENSION].

    PubMed

    Lazutkina, A Y; Gorbunov, V V

    2016-01-01

    The paper reports results of 6 year prospective observation of 7959 members of locomotive crews engaged at the Transbaikal Railways. The study aimed to estimate the probability and time of development of resistant arterial hypertension under effect of predictors of this disease. The data obtained are of value for diagnostic, prophylactic, and therapeutic practice. PMID:27522725

  11. Carbamazepine-induced hypertension: A rare case

    PubMed Central

    Kharb, Preeti; Mittal, Niti; Gupta, Mahesh C.

    2015-01-01

    A 74-year-old female with trigeminal neuralgia developed hypertension after the initiation of carbamazepine therapy. The time sequence of start of the suspected drug and onset of hypertension are consistent with the diagnosis. The hypertension did not resolve with antihypertensive therapy or dose reduction of carbamazepine. Patient recovered after the carbamazepine therapy was discontinued. The positive rechallenge and positive dechallenge showed association of carbamazepine therapy with hypertension as its adverse effect. This is a rare case that we report of carbamazepine-induced hypertension and this report may act as alerting mechanism to the health care professionals especially neurologists. PMID:26816475

  12. Cardiovascular magnetic resonance in systemic hypertension

    PubMed Central

    2012-01-01

    Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053

  13. Magnetic Resonance Imaging in Pediatric Pulmonary Hypertension

    PubMed Central

    Olgunturk, Rana; Cevik, Ayhan; Terlemez, Semiha; Kacar, Emre; Oner, Yusuf Ali

    2015-01-01

    The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ≥25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ≥1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ≥25 mm. PMID:26175631

  14. Magnetic resonance imaging in pediatric pulmonary hypertension.

    PubMed

    Pektas, Ayhan; Olgunturk, Rana; Cevik, Ayhan; Terlemez, Semiha; Kacar, Emre; Oner, Yusuf Ali

    2015-06-01

    The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ≥25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ≥1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ≥25 mm. PMID:26175631

  15. The diagnosis and management of hypertensive crises.

    PubMed

    Varon, J; Marik, P E

    2000-07-01

    Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP. PMID:10893382

  16. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension

    PubMed Central

    Patel, Sheila K.; Velkoska, Elena; Freeman, Melanie; Wai, Bryan; Lancefield, Terase F.; Burrell, Louise M.

    2014-01-01

    Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial

  17. Endothelial dysfunction in DOCA-salt-hypertensive mice: role of neuronal nitric oxide synthase-derived hydrogen peroxide.

    PubMed

    Silva, Grazielle C; Silva, Josiane F; Diniz, Thiago F; Lemos, Virginia S; Cortes, Steyner F

    2016-06-01

    Endothelial dysfunction is a common problem associated with hypertension and is considered a precursor to the development of micro- and macro-vascular complications. The present study investigated the involvement of nNOS (neuronal nitric oxide synthase) and H2O2 (hydrogen peroxide) in the impaired endothelium-dependent vasodilation of the mesenteric arteries of DOCA (deoxycorticosterone acetate)-salt-hypertensive mice. Myograph studies were used to investigate the endothelium-dependent vasodilator effect of ACh (acetylcholine). The expression and phosphorylation of nNOS and eNOS (endothelial nitric oxide synthase) were studied by Western blot analysis. Immunofluorescence was used to examine the localization of nNOS and eNOS in the endothelial layer of the mesenteric artery. The vasodilator effect of ACh is strongly impaired in mesenteric arteries of DOCA-salt-hypertensive mice. Non-selective inhibition of NOS sharply reduced the effect of ACh in both DOCA-salt-hypertensive and sham mice. Selective inhibition of nNOS and catalase led to a higher reduction in the effect of ACh in sham than in DOCA-salt-hypertensive mice. Production of H2O2 induced by ACh was significantly reduced in vessels from DOCA-salt-hypertensive mice, and it was blunted after nNOS inhibition. The expression of both eNOS and nNOS was considerably lower in DOCA-salt-hypertensive mice, whereas phosphorylation of their inhibitory sites was increased. The presence of nNOS was confirmed in the endothelial layer of mesenteric arteries from both sham and DOCA-salt-hypertensive mice. These results demonstrate that endothelial dysfunction in the mesenteric arteries of DOCA-salt-hypertensive mice is associated with reduced expression and functioning of nNOS and impaired production of nNOS-derived H2O2 Such findings offer a new perspective for the understanding of endothelial dysfunction in hypertension. PMID:26976926

  18. [Hypertensive crises in patients with arterial hypertension in ambulatory treatment].

    PubMed

    Gomes Guedes, Nirla; Chaves Costa, Francisca Bertilia; Moreira, Rafaella Pessoa; Moreira, Tahissa Frota; Soares Chavess, Emilia; de Araújo, Thelma Leite

    2005-06-01

    This study assessed the sociodemographic characteristics and the characteristics of therapeutic adhesion of 27 bearers of arterial hypertension undergoing ambulatorial treatment who had hypertensive urgencies crises or emergencies in the city of Fortaleza in the period between October of 2002 and May of 2003. The majority were women, between 50 and 60-years old, with little formal education, treatment time shorter than 5 years and time of diagnosis varying from 5 to 10 years. The use of medicine was the treatment that was most mentioned, followed by the reduction of the consumption of salt and attendance to medical appointments. However, attending the appointments and receiving orientation did not seem to change their behavior, since most of the patients that were interviewed practiced no physical exercises and demonstrated little knowledge of the illness, for they attributed the rise of the arterial pressure to emotional factors. PMID:16060305

  19. The change and significance of the Na+-K+-ATPase alpha-subunit in ouabain-hypertensive rats.

    PubMed

    Tian, G; Dang, C; Lu, Z

    2001-11-01

    Ouabain has recently been identified as an endogenous Na+-K+ pump inhibitor having a close association with hypertension. However, some patients with hypertention do not show high levels of endogenous ouabain (EO), and patients with high EO levels do not necessarily suffer from hypertention. It is believed that the Na+-K+-ATPase activity in essential hypertension does not undergo homogenous change. The present study was designed, therefore, to investigate the expression and the significance of the Na+-K+-ATPase alpha-subunit isoforms in kidney tissue in ouabain-hypertensive rats. Ouabain was administered chronically to establish a model of ouabain-hypertensive rats. Biochemical analysis, cytobiology and sABC immunohistochemistry were they used to assay for expression of Na+-K+-ATPase alpha-subunit isoforms in kidney tissue. After the first week of receiving ouabain, 65% (n=13) of rats had hypertension. After the second week, the blood pressure of these 13 hypertensive rats was increased significantly compared to the baseline and control levels (p<0.05). The plasma renin activity was normal, and angiotensin II and aldosterone levels were increased significantly in these rats (p<0.05). But in the other 35% (n=7) of rats of the experimental group, there was no apparent increase in blood pressure after receiving ouabain. The plasma ouabain level in the non-hypertensive subgroup was significantly higher than that in the hypertensive subgroup, but the 86Rb intake and the number of 3H-ouabain binding sites did not decrease. The Na+-K+-ATPase activity showed non-homogeneous changes. In hypertensive rats, the expression levels of ouabain paralleled the degree of hypertension (r=0.88, p<0.05). The positive granules were mainly scattered in the cytoblastoma of the reticular zone of adrenal cortex. There were thus different levels of expression of Na+-K+-ATPase alpha-subunit isoforms in this model. In the hypertension subgroup the alpha1 was most strongly expressed, followed

  20. Estimating the Prevalence and Awareness Rates of Hypertension in Africa: A Systematic Analysis

    PubMed Central

    Adeloye, Davies; Basquill, Catriona

    2014-01-01

    Background The burden of hypertension is high in Africa, and due to rapid population growth and ageing, the exact burden on the continent is still far from being known. We aimed to estimate the prevalence and awareness rates of hypertension in Africa based on the cut off “≥140/90 mm Hg”. Methods We conducted a systematic search of Medline, EMBASE and Global Health. Search date was set from January 1980 to December 2013. We included population-based studies on hypertension, conducted among people aged ≥15 years and providing numerical estimates on the prevalence of hypertension in Africa. Overall pooled prevalence of hypertension in mixed, rural and urban settings in Africa were estimated from reported crude prevalence rates. A meta-regression epidemiological modelling, using United Nations population demographics for the years 1990, 2000, 2010 and 2030, was applied to determine the prevalence rates and number of cases of hypertension in Africa separately for these four years. Results Our search returned 7680 publications, 92 of which met the selection criteria. The overall pooled prevalence of hypertension in Africa was 19.7% in 1990, 27.4% in 2000 and 30.8% in 2010, each with a pooled awareness rate (expressed as percentage of hypertensive cases) of 16.9%, 29.2% and 33.7%, respectively. From the modelling, over 54.6 million cases of hypertension were estimated in 1990, 92.3 million cases in 2000, 130.2 million cases in 2010, and a projected increase to 216.8 million cases of hypertension by 2030; each with an age-adjusted prevalence of 19.1% (13.9, 25.5), 24.3% (23.3, 31.6), 25.9% (23.5, 34.0), and 25.3% (24.3, 39.7), respectively. Conclusion Our findings suggest the prevalence of hypertension is increasing in Africa, and many hypertensive individuals are not aware of their condition. We hope this research will prompt appropriate policy response towards improving the awareness, control and overall management of hypertension in Africa. PMID:25090232

  1. Hypertension in Malaysia: An Analysis of Trends From the National Surveys 1996 to 2011.

    PubMed

    Naing, Cho; Yeoh, Peng Nam; Wai, Victor Nyunt; Win, Ni Ni; Kuan, Lai Pei; Aung, Kyan

    2016-01-01

    This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia.The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable.Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%-35.8%) in 1996, 42.6% (37.5%-43.5%) in 2006, and 43.5% (40.4%-46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P < 0.001) and of 29% from 1996 to 2006 (P < 0.05), but only a small change of 1% from 2006 to 2011 (P = 0.6). For population ≥18 years, only a 1% increase in prevalence of hypertension occurred from the 2006 NHMS (32.2%) to the 2011 NHMS (32.7%) (P = 0.25). A relative increase of 13% occurred in those with primary education (P < 0.001) and a 15% increase was seen in those with secondary education (P < 0.001). The rate of increase in the prevalence of hypertension in the population with income level RM 3000-3999 was the highest (18%) during this period. In general, the older age group had higher prevalence of hypertension in the 2006 and 2011 NHMSs. The prevalence peaked at 74.1% among population aged 65 to 69 years in the 2011 NHMS. Both the proportion of awareness and the control of hypertension in Malaysia improved from 1996 to 2006. A change in the control of hypertension was 13% higher in women than in men.The findings suggest that the magnitude of

  2. Long Noncoding RNA-GAS5: A Novel Regulator of Hypertension-Induced Vascular Remodeling.

    PubMed

    Wang, Yang-Ning-Zhi; Shan, Kun; Yao, Mu-Di; Yao, Jin; Wang, Jia-Jian; Li, Xiang; Liu, Ban; Zhang, Yang-Yang; Ji, Yong; Jiang, Qin; Yan, Biao

    2016-09-01

    Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension. PMID:27432865

  3. Role for Telomerase in Pulmonary Hypertension

    PubMed Central

    Abid, Shariq; Quarck, Rozenn; Marcos, Elisabeth; Parpaleix, Aurelien; Gary-Bobo, Guillaume; Dubois-Randé, Jean-Luc; Derumeaux, Geneviève; Boczkowski, Jorge; Delcroix, Marion; Blasco, Maria A.; Lipskaia, Larissa; Amsellem, Valérie; Adnot, Serge

    2015-01-01

    Background Cells exhibiting dysregulated growth may express telomerase reverse transcriptase (TERT), the dual function of which consists of maintaining telomere length, in association with the RNA template molecule TERC, and controlling cell growth. Here, we investigated lung TERT in human and experimental pulmonary hypertension (PH) and its role in controlling pulmonary artery smooth muscle cell (PA-SMC) proliferation. Methods and Results Marked TERT expression or activity was found in lungs from patients with idiopathic PH and from mice with PH induced by hypoxia or serotonin-transporter overexpression (SM22-5HTT+ mice), chiefly within PA-SMCs. In cultured mouse PA-SMCs, TERT was expressed on growth stimulation by serum. The TERT inhibitor imetelstat and the TERT activator TA65 abrogated and stimulated PA-SMC growth, respectively. PA-SMCs from PH mice showed a heightened proliferative phenotype associated with increased TERT expression, which was suppressed by imetelstat treatment. TERC−/− mice at generation 2 and TERT−/− mice at generations 2, 3, and 4 developed less severe PH than did wild-type mice exposed to chronic hypoxia, with less distal pulmonary artery muscularization and fewer Ki67-stained proliferating PA-SMCs. Telomere length differed between TERC−/− and TERT−/− mice, whereas PH severity was similar in the 2 strains and across generations. Chronic imetelstat treatment reduced hypoxia-induced PH in wild-type mice or partially reversed established PH in SM22-5HTT+ mice while simultaneously decreasing TERT expression. Opposite effects occurred in mice treated with TA65. Conclusions Telomerase exerts telomere-independent effects on PA-SMC growth in PH and may constitute a treatment target for PH. PMID:25550449

  4. Hypertensive urgency: an important aetiology of rebound hypertension.

    PubMed

    Malaty, John; Malaty, Irene A

    2014-01-01

    A 46-year-old African-American man with a history of hypertension, end-stage kidney disease (on haemodialysis) and previous cocaine misuse presented to the emergency room with a sudden onset of severe headache and diaphoresis without other neurological or cardiovascular signs/symptoms. He checked his blood pressure at home and found it to be 230/130. It did not improve despite taking two serial doses of oral clonidine 0.3 mg. Evaluation with head CT and lumbar puncture demonstrated no acute intracranial process, such as subarachnoid haemorrhage. These symptoms started after he took Libido-Max, an over-the-counter supplement for erectile dysfunction. This supplement includes yohimbine, an α-2 antagonist, which counteracts the effects of oral clonidine, one of his routine antihypertensive medications. This led to rebound hypertension and made his hypertensive urgency resistant to oral clonidine. He was successfully treated with intravenous labetalol and his symptoms quickly resolved after lowering of his blood pressure. PMID:25336552

  5. Heme oxygenase system and hypertension: a comprehensive insight.

    PubMed

    Tiwari, Shuchita; Ndisang, Joseph Fomusi

    2014-01-01

    Hypertension is a complex interplay of interrelated etiologies, and the leading risk factor for many cardiovascular morbidity and mortality worldwide. Cardinal pathophysiological features of hypertension include enhanced vascular inflammation, vascular remodeling, vascular contractility and increased oxidative stress. In response to oxidative, inflammatory or other noxious stimuli, many physiological pathways like the heme oxygenase (HO) system are activated in an attempt to counteract tissue insults. However, the pathophysiological activation of the HO system only results to a transient increase of HO activity that fall below the necessary threshold capable of activating the downstream signaling components of the HO system like the soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) secondary messenger system. Therefore, a more robust potentiation of the HO system by pharmacological agents such as hemin, heme-arginate, cobalt protoporphyrin or through retroviral HO-1 gene delivery would be needed to surmount the threshold for cytoprotection. The HO system modulates cellular homeostasis. Importantly, the HO system plays a vital role in a wide spectrum of physiologic including the regulation of blood vessel tone. Alterations in the activity and expression of HO has been correlated to pathophysiology of hypertension and related complications such as hypertrophy, myocardial infarction and heart failure. Moreover, the cytoprotection exerted by HO is attributable to its catabolic products namely, carbon monoxide, bilirubin/biliverdin, and ferritin that are known to modulate immune, inflammatory and oxidative insults. The growing incidence of hypertension and associated cardiometabolic complications has prompted the need for the exploration of alternative therapeutic strategies like substances capable of potentiating the HO system. This review briefly, highlights the functional significance of the HO system and its downstream signaling molecules

  6. Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension.

    PubMed

    Bunbupha, Sarawoot; Prachaney, Parichat; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Welbat, Jariya Umka; Pakdeechote, Poungrat

    2015-11-01

    A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities. PMID:26234646

  7. Emergency Management of Hypertension in Children

    PubMed Central

    Singh, Dinesh; Akingbola, Olugbenga; Yosypiv, Ihor; El-Dahr, Samir

    2012-01-01

    Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information. PMID:22577545

  8. The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats

    PubMed Central

    Moreno, Enrique; Moral-Sanz, Javier; Barreira, Bianca; Galindo, Pilar; Pandolfi, Rachele; Jimenez, Rosario; Moreno, Laura; Cogolludo, Angel; Duarte, Juan; Perez-Vizcaino, Francisco

    2014-01-01

    Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH. PMID:25460361

  9. Treatment of pediatric pulmonary hypertension

    PubMed Central

    Hawkins, Amy; Tulloh, Robert

    2009-01-01

    Pulmonary hypertension was once thought to be a rare condition and only managed in specialized centers. Now however, with the advent of echocardiography, it is found in many clinical scenarios, in the neonate with chronic lung disease, in the acute setting in the intensive care unit, in connective tissue disease and in cardiology pre- and postoperatively. We have a better understanding of the pathological process and have a range of medication which is starting to be able to palliate this previously fatal condition. This review describes the areas that are known in this condition and those that are less familiar. The basic physiology behind pulmonary hypertension and pulmonary vascular disease is explained. The histopathologic process and the various diagnostic tools are described and are followed by the current and future therapy at our disposal. PMID:19554091

  10. Pulmonary Hypertension: Types and Treatments

    PubMed Central

    Rose-Jones, Lisa J; Mclaughlin, Vallerie V

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmo-nary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario. PMID:24251459

  11. Hypertensive emergencies: diagnosis and management.

    PubMed

    Phillips, Robert A; Greenblatt, Jonathan; Krakoff, Lawrence R

    2002-01-01

    The treatment of hypertension is preventive medicine. This principle applies in the emergency room as well as the clinic. However, there are crucial contrasts between these two care settings related to specific goals of management for real emergencies and nonemergency conditions. In the emergency room, rapid triage is necessary to separate those who can safely be sent home for future clinic assessment from those who require immediate interventions including short stays in 24-hour observation units or hospitalization for more serious problems. This review focuses on decisions related to hypertension management in the emergency room and over brief periods of observation and treatment. Strategy is supported by evidence-based considerations whenever possible. Where outcome studies are not available, we rely on the rationale derived from relevant clinical research. PMID:12138413

  12. [Abdominal bruit associated with hypertension].

    PubMed

    Fontseré, N; Bonet, J; Bonal, J; Romero, R

    2004-01-01

    First cause of secondary hypertension is renovascular hypertension which presents abdominal bruit in 16 to 20% of cases. This clinical sign is also associated with other vascular disease of the abdomen such as celiac trunk stenosis and/or aneurysms located on the pancreaticoduodenal or gastroduodenal arcs level, with little representation among aneurysm. They usually appear on a context of digestive complications like neoplasias, chronic pancreatitis or gastric obstructions possibly with obstructive icterus, hemorrhage and acute abdomen episodes. Its presentation in other contexts is rare and constitutes a diagnostic challenge. Diagnosis is made by abdominal arteriography which is the best method because you can locate the problem as well as intervene therapeutically with embolization of the aneurysme. We would like to emphasize the importance of a quick diagnosis due to the risk of rupture and the high morbi-mortality associated. PMID:15219082

  13. Obligatory Role for B Cells in the Development of Angiotensin II-Dependent Hypertension.

    PubMed

    Chan, Christopher T; Sobey, Christopher G; Lieu, Maggie; Ferens, Dorota; Kett, Michelle M; Diep, Henry; Kim, Hyun Ah; Krishnan, Shalini M; Lewis, Caitlin V; Salimova, Ekaterina; Tipping, Peter; Vinh, Antony; Samuel, Chrishan S; Peter, Karlheinz; Guzik, Tomasz J; Kyaw, Tin S; Toh, Ban-Hock; Bobik, Alexander; Drummond, Grant R

    2015-11-01

    Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-β expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by ≈35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension. PMID:26351030

  14. Hippocampal neurogenesis response: What can we expect from two different models of hypertension?

    PubMed

    Pedroso, Daniela; Nunes, Ana R; Diogo, Lucília N; Oudot, Carole; Monteiro, Emília C; Brenner, Catherine; Vieira, Helena L A

    2016-09-01

    Hypertension is associated with cerebrovascular disease, white matter lesion and cognitive deficit, both in experimental models and clinical observations. Furthermore, in non-clinical models it is shown that hippocampus is affected by hypertension and hypoxia. Herein, two distinct hypertension models were used to study neurogenic response in hippocampus. Dahl salt sensitive (DSS) rat model is a genetic based idiopathic model, while chronic intermittent hypoxia (CIH) mimics the hypertension observed in patients with obstructive sleep apnea (OSA). Both models are chronic and trigger hypertension. No macroscopic alterations based on histological analysis were found in hippocampus derived from DSS and CIH exposure rats. Nevertheless, in hippocampus derived from CIH-induced hypertensive rats, there was a decrease on neuronal population (MAP2 and NeuN positive cells) and an increase on astrocytic marker GFAP. Accordingly, a higher increase on Ki67 expressing cells was found in dentate gyrus (DG) region, suggesting an enhancement of cell proliferation, concomitantly with an increase of Nestin staining, which indicates the presence of immature neurons under differentiation. While, in hippocampus of DSS rats with or without high salt diet, there was no remarkable difference indicating potential neuronal loss, astrocytic activation or neurogenesis. Furthermore, in both models hypertension did not alter the levels of expression of the stress response enzyme heme oxygenase-1 in DG. These data indicate that intermittent hypoxia might be the key factor involved in neurogenesis modulation in hippocampus. Furthermore, two hypotheses can be explored: (i) activation of neurogenesis is a response against neuronal loss induced by hypertension and/or hypoxia or (ii) neurogenesis can be directly stimulated by hypoxia as a neuroprotective mechanism. PMID:27235865

  15. [Hypertension, endothelial dysfunction and cardiovascular risk].

    PubMed

    Nitenberg, A

    2006-10-01

    Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events. PMID:17100143

  16. ATROPHIC CARDIOMYOCYTE SIGNALING IN HYPERTENSIVE HEART DISEASE

    PubMed Central

    Kamalov, German; Zhao, Wenyuan; Zhao, Tieqiang; Sun, Yao; Ahokas, Robert A.; Marion, Tony N.; Darazi, Fahed Al; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2013-01-01

    Cardinal pathologic features of hypertensive heart disease (HHD) include not only hypertrophied cardiomyocytes and foci of scattered microscopic scarring, a footprint of prior necrosis, but also small myocytes ensnared by fibrillar collagen where disuse atrophy with protein degradation would be predicted. Whether atrophic signaling is concordant with the appearance of HHD and involves oxidative and endoplasmic reticulum (ER) stress remains unexplored. Herein, we examine these possibilities focusing on the left ventricle (LV) and cardiomyocytes harvested from hypertensive rats receiving 4 wks aldosterone/salt treatment (ALDOST) alone or together with ZnSO4, a nonvasoactive antioxidant, with the potential to attenuate atrophy and optimize hypertrophy. Compared to untreated age-/sex-/strain-matched controls, ALDOST was accompanied by: a) LV hypertrophy with preserved systolic function; b) concordant cardiomyocyte atrophy (<1000 μm2) found at sites bordering on fibrosis where they were re-expressing β-myosin heavy chain; and c) upregulation of ubiquitin ligases, MuRF1 and atrogin-1, and elevated 8-isoprostane and unfolded protein ER response with mRNA upregulation of stress markers. ZnSO4 cotreatment reduced lipid peroxidation, fibrosis and the number of atrophic myocytes, together with a further increase in cell area and width of atrophied and hypertrophied myocytes, and improved systolic function, but did not attenuate elevated blood pressure. We conclude that atrophic signaling, concordant with hypertrophy, occurs in the presence of a reparative fibrosis and induction of oxidative and ER stress at sites of scarring where myocytes are atrophied. ZnSO4 cotreatment in HHD with ALDOST attenuates the number of atrophic myocytes, optimizes size of atrophied and hypertrophied myocytes, and improves systolic function. PMID:24084216

  17. Endoscopic Management of Portal Hypertension

    PubMed Central

    Al-Busafi, Said A.; Ghali, Peter; Wong, Philip; Deschenes, Marc

    2012-01-01

    Cirrhosis is the leading cause of portal hypertension worldwide, with the development of bleeding gastroesophageal varices being one of the most life-threatening consequences. Endoscopy plays an indispensible role in the diagnosis, staging, and prophylactic or active management of varices. With the expected future refinements in endoscopic technology, capsule endoscopy may one day replace traditional gastroscopy as a diagnostic modality, whereas endoscopic ultrasound may more precisely guide interventional therapy for gastric varices. PMID:22830037

  18. [Neonatal intermittent hypoxia and hypertension].

    PubMed

    Sukhova, G K; Nozdrachev, A D; Gozal, D

    2009-01-01

    Obstructive apnea during sleep is accompanied by intermittent hypoxia (IH) leading to hypertension and other cardiovascular disturbances. A comparative evaluation of long-term effects of the neonatal IH on the cardiovascular function was performed in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR). The newborn rats were placed for 30 days to conditions of IH (8 and 21% O2, alternating every 90 s for 12 h/day). Control groups of rats were constantly kept in normoxia. By 6 months, in the spontaneously hypertensive rats submitted to IH at the period of wakefulness there was a statistically significant increase (as compared with control) of the systolic (correspondingly 185.8 +/- 1.7 and 169.9 +/- 1.4 mm Hg, p < 0.01) and diastolic pressure (correspondingly 96.2 +/- 4.9 and 86.0 +/- 2.6 mm Hg, p < 0.01). During sleep, the systolic and diastolic pressure in these rats was higher than in control animals by 10 mm Hg (p < 0.01) and 12 mm Hg (p < 0.01), its decrease during sleep being absent. SHR submitted to IH had an increase in low- to the high-frequency power ratio of the heart rate variability from 0.9 +/- 0.15 to 1.5 +/- 0.17, which indicates a shift of the sympatho-parasympathetic balance in this group towards predominance of the sympathetic component. In the Sprague-Dawley rats submitted to neonatal hypoxia, the above changes were not pronounced. These peculiarities of the hypertensive rats allow establishing connection of the genetic factor with the sympathetic mechanism providing long-term consequences of the neonatal IH for the cardiovascular control in these rats. PMID:19435263

  19. Review of new hypertension guidelines.

    PubMed

    Zhang, P-Y

    2015-01-01

    The Eighth Joint National Committee (JNC 8) released its new guidelines on the management of adult hypertension in Dec 2013. The key departures from JNC 7 include target blood pressures and thresholds for initiation of elderly patients and in patients under age 60 with diabetes and kidney disease. In this review, we analyse the critical questions, basis of new recommendations, major deviations from JNC 7, the strengths and limitations of changes in previous management guidelines. PMID:25683948

  20. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies. PMID:26070575

  1. Vascular smooth muscle in hypertension.

    PubMed

    Winquist, R J; Webb, R C; Bohr, D F

    1982-06-01

    The cause of the elevated arterial pressure in most forms of hypertension is an increase in total peripheral resistance. This brief review is directed toward an assessment of recent investigations contributing information about the factors responsible for this increased vascular resistance. Structural abnormalities in the vasculature that characterize the hypertensive process are 1) changes in the vascular media, 2) rarefication of the resistance vessels, and 3) lesions of the intimal vascular surface. These abnormalities are mainly the result of an adaptive process and are secondary to the increase in wall stress and/or to pathological damage to cellular components in the vessel wall. Functional alterations in the vascular smooth muscle are described as changes in agonist-smooth muscle interaction or plasma membrane permeability. These types of changes appear to play a primary, initiating role in the elevation of vascular resistance of hypertension. These alterations are not the result of an increase in wall stress and they often precede the development of high blood pressure. The functional changes are initiated by abnormal function of neurogenic, humoral, and/or myogenic changes that alter vascular smooth muscle activity. PMID:6282652

  2. [Mexican consensus on portal hypertension].

    PubMed

    Narváez-Rivera, R M; Cortez-Hernández, C A; González-González, J A; Tamayo-de la Cuesta, J L; Zamarripa-Dorsey, F; Torre-Delgadillo, A; Rivera-Ramos, J F J; Vinageras-Barroso, J I; Muneta-Kishigami, J E; Blancas-Valencia, J M; Antonio-Manrique, M; Valdovinos-Andraca, F; Brito-Lugo, P; Hernández-Guerrero, A; Bernal-Reyes, R; Sobrino-Cossío, S; Aceves-Tavares, G R; Huerta-Guerrero, H M; Moreno-Gómez, N; Bosques-Padilla, F J

    2013-01-01

    The aim of the Mexican Consensus on Portal Hypertension was to develop documented guidelines to facilitate clinical practice when dealing with key events of the patient presenting with portal hypertension and variceal bleeding. The panel of experts was made up of Mexican gastroenterologists, hepatologists, and endoscopists, all distinguished professionals. The document analyzes themes of interest in the following modules: preprimary and primary prophylaxis, acute variceal hemorrhage, and secondary prophylaxis. The management of variceal bleeding has improved considerably in recent years. Current information indicates that the general management of the cirrhotic patient presenting with variceal bleeding should be carried out by a multidisciplinary team, with such an approach playing a major role in the final outcome. The combination of drug and endoscopic therapies is recommended for initial management; vasoactive drugs should be started as soon as variceal bleeding is suspected and maintained for 5 days. After the patient is stabilized, urgent diagnostic endoscopy should be carried out by a qualified endoscopist, who then performs the corresponding endoscopic variceal treatment. Antibiotic prophylaxis should be regarded as an integral part of treatment, started upon hospital admittance and continued for 5 days. If there is treatment failure, rescue therapies should be carried out immediately, taking into account that interventional radiology therapies are very effective in controlling refractory variceal bleeding. These guidelines have been developed for the purpose of achieving greater clinical efficacy and are based on the best evidence of portal hypertension that is presently available. PMID:23664429

  3. A Panel of Stably Expressed Reference Genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos)

    PubMed Central

    Chapman, Joanne R.; Helin, Anu S.; Wille, Michelle; Atterby, Clara; Järhult, Josef D.; Fridlund, Jimmy S.; Waldenström, Jonas

    2016-01-01

    Determining which reference genes have the highest stability, and are therefore appropriate for normalising data, is a crucial step in the design of real-time quantitative PCR (qPCR) gene expression studies. This is particularly warranted in non-model and ecologically important species for which appropriate reference genes are lacking, such as the mallard—a key reservoir of many diseases with relevance for human and livestock health. Previous studies assessing gene expression changes as a consequence of infection in mallards have nearly universally used β-actin and/or GAPDH as reference genes without confirming their suitability as normalisers. The use of reference genes at random, without regard for stability of expression across treatment groups, can result in erroneous interpretation of data. Here, eleven putative reference genes for use in gene expression studies of the mallard were evaluated, across six different tissues, using a low pathogenic avian influenza A virus infection model. Tissue type influenced the selection of reference genes, whereby different genes were stable in blood, spleen, lung, gastrointestinal tract and colon. β-actin and GAPDH generally displayed low stability and are therefore inappropriate reference genes in many cases. The use of different algorithms (GeNorm and NormFinder) affected stability rankings, but for both algorithms it was possible to find a combination of two stable reference genes with which to normalise qPCR data in mallards. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies in ducks. The fact that nearly all previous studies of the influence of pathogen infection on mallard gene expression have used a single, non-validated reference gene is problematic. The toolkit of putative reference genes provided here offers a solid foundation for future studies of gene expression in mallards and other waterfowl. PMID:26886224

  4. Global Earthquake and Volcanic Eruption Economic losses and costs from 1900-2014: 115 years of the CATDAT database - Trends, Normalisation and Visualisation

    NASA Astrophysics Data System (ADS)

    Daniell, James; Skapski, Jens-Udo; Vervaeck, Armand; Wenzel, Friedemann; Schaefer, Andreas

    2015-04-01

    Over the past 12 years, an in-depth database has been constructed for socio-economic losses from earthquakes and volcanoes. The effects of earthquakes and volcanic eruptions have been documented in many databases, however, many errors and incorrect details are often encountered. To combat this, the database was formed with socioeconomic checks of GDP, capital stock, population and other elements, as well as providing upper and lower bounds to each available event loss. The definition of economic losses within the CATDAT Damaging Earthquakes Database (Daniell et al., 2011a) as of v6.1 has now been redefined to provide three options of natural disaster loss pricing, including reconstruction cost, replacement cost and actual loss, in order to better define the impact of historical disasters. Similarly for volcanoes as for earthquakes, a reassessment has been undertaken looking at the historical net and gross capital stock and GDP at the time of the event, including the depreciated stock, in order to calculate the actual loss. A normalisation has then been undertaken using updated population, GDP and capital stock. The difference between depreciated and gross capital can be removed from the historical loss estimates which have been all calculated without taking depreciation of the building stock into account. The culmination of time series from 1900-2014 of net and gross capital stock, GDP, direct economic loss data, use of detailed studies of infrastructure age, and existing damage surveys, has allowed the first estimate of this nature. The death tolls in earthquakes from 1900-2014 are presented in various forms, showing around 2.32 million deaths due to earthquakes (with a range of 2.18 to 2.63 million) and around 59% due to masonry buildings and 28% from secondary effects. For the death tolls from the volcanic eruption database, 98000 deaths with a range from around 83000 to 107000 is seen from 1900-2014. The application of VSL life costing from death and injury

  5. Resistant Hypertension Workup and Approach to Treatment

    PubMed Central

    Makris, Anastasios; Seferou, Maria; Papadopoulos, Dimitris P.

    2011-01-01

    Resistant hypertension is defined as blood pressure above the patient's goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic. Evaluation of patients with resistive hypertension should first confirm that they have true resistant hypertension by ruling out or correcting factors associated with pseudoresistance such as white coat hypertension, suboptimal blood pressure measurement technique, poor adherence to prescribed medication, suboptimal dosing of antihypertensive agents or inappropriate combinations, the white coat effect, and clinical inertia. Management includes lifestyle and dietary modification, elimination of medications contributing to resistance, and evaluation of potential secondary causes of hypertension. Pharmacological treatment should be tailored to the patient's profile and focus on the causative pathway of resistance. Patients with uncontrolled hypertension despite receiving an optimal therapy are candidates for newer interventional therapies such as carotid baroreceptor stimulation and renal denervation. PMID:21234416

  6. Managing Hypertension in the Newborn Infants

    PubMed Central

    Nickavar, Azar; Assadi, Farahnak

    2014-01-01

    Hypertension in newborn infants, particularly those requiring intensive care, is becoming increasingly recognized, with prevalence of 0.2-3%. Recent studies have established normative tables for blood pressure (BP) in both term and pre-term infants based on the gestational age, postnatal age, gender, weight and height, identifying the neonates at increased risk for early-onset cardiovascular disease. Common causes of neonatal hypertension include thromboembolic complications secondary to umbilical artery catheterization, congenital renal structural malformation, renovascular disease, aortic coarctation, as well as acute kidney injury and certain medications. A careful diagnostic evaluation should lead to identification of the underlying cause of hypertension in most infants. Treatment options should be tailored to the severity; and underlying cause of hypertension, including intravenous and/or oral therapy. This review summarizes recent work in these areas, focusing on optimal BP measurement, definition, evaluation and management of hypertension as well as advances in drug therapy of neonatal hypertension. PMID:24791189

  7. Current diagnosis and management of hypertensive emergency.

    PubMed

    Haas, Andrew R; Marik, Paul E

    2006-01-01

    The appropriate and timely evaluation and treatment of patients with severely elevated blood pressure is essential to avoid serious adverse outcomes. Most importantly, the distinction between a hypertensive emergency (crisis) and urgency needs to be made. A sudden elevation in systolic (SBP) and/or diastolic blood pressure (DBP) that is associated with acute end organ damage (cardiovascular, cerebrovascular, or renal) is defined as a hypertensive crisis or emergency. In contrast, acute elevation in SBP and/or DBP not associated with evidence of end organ damage is defined as hypertensive urgency. In patients with a hypertensive emergency, blood pressure control should be attained as expeditiously as possible with parenteral medications to prevent ongoing and potentially permanent end organ damage. In contrast, with hypertensive urgency, blood pressure control can be achieved with the use of oral medications within 24-48 hours. This paper reviews the management of hypertensive emergencies. PMID:17150051

  8. Pharmacologic treatment of hypertensive disorders during pregnancy.

    PubMed

    Yankowitz, Jerome

    2004-01-01

    Pregnancy complicated by hypertension is a common problem faced by clinicians. It can lead to substantial maternal and/or fetal/neonatal morbidity and mortality. There are a variety of medications that can be used during pregnancy either for treatment of significant chronic hypertension or in cases of acute severe hypertension. Most antihypertensive drugs have been shown to be safe for use in pregnancy. A variety of medications are available to treat more severe hypertension, although the use of pharmacologic therapy to treat mild chronic hypertension during pregnancy has not been supported in the literature. The data are more limited concerning drugs that would be used in the event of hypertensive emergencies or in an intensive care setting; however, in such a situation, maternal health and life become paramount and, despite lack of good studies, appropriate treatment should be rendered. PMID:15478474

  9. [Diagnosis and treatment of ocular hypertension].

    PubMed

    Sun, Y Y; Chen, W W; Wang, N L

    2016-07-01

    Ocular hypertension is popular among people, with a prevalence of 3% to 10% in those older than 40 years old. Without proper intervention, over 10% of the patients with ocular hypertension would develop glaucoma in the following 5 to 10 years. Glaucoma has become one of the leading causes of blindness all over the world, which makes it essential for us to pay enough attention to the prevention and treatment of ocular hypertension. However, it is not cost-effective to treat all the patients with ocular hypertension. Certain side effects may also be caused with long-term medical treatment. Therefore, it is of great importance for ophthalmologists to identify the right time and use appropriate therapeutic methods. To introduce the knowledge of ocular hypertension, the definition, epidemiology, diagnosis, risk factors and treatment of ocular hypertension are reviewed in this article. (Chin J Ophthalmol, 2016, 52: 542-546). PMID:27531115

  10. The hypothalamic neuropeptide FF network is impaired in hypertensive patients

    PubMed Central

    Goncharuk, Valeri D; Buijs, Ruud M; Jhamandas, Jack H; Swaab, Dick F

    2014-01-01

    Background The human hypothalamus contains the neuropeptide FF (NPFF) neurochemical network. Animal experiments demonstrated that NPFF is implicated in the central cardiovascular regulation. We therefore studied expression of this peptide in the hypothalamus of individuals who suffered from essential hypertension (n = 8) and died suddenly due to acute myocardial infarction (AMI), and compared to that of healthy individuals (controls) (n = 6) who died abruptly due to mechanical trauma of the chest. Methods The frozen right part of the hypothalamus was cut coronally into serial sections of 20 μm thickness, and each tenth section was stained immunohistochemically using antibody against NPFF. The central section through each hypothalamic nucleus was characterized by the highest intensity of NPFF immunostaining and thus was chosen for quantitative densitometry. Results In hypertensive patients, the area occupied by NPFF immunostained neuronal elements in the central sections through the suprachiasmatic nucleus (SCh), paraventricular hypothalamic nucleus (Pa), bed nucleus of the stria terminalis (BST), perinuclear zone (PNZ) of the supraoptic nucleus (SON), dorso- (DMH), ventromedial (VMH) nuclei, and perifornical nucleus (PeF) was dramatically decreased compared to controls, ranging about six times less in the VMH to 15 times less in the central part of the BST (BSTC). The NPFF innervation of both nonstained neuronal profiles and microvasculature was extremely poor in hypertensive patients compared to control. Conclusions The decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease. PMID:25161813

  11. Upregulated Copper Transporters in Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Zimnicka, Adriana M.; Tang, Haiyang; Guo, Qiang; Kuhr, Frank K.; Oh, Myung-Jin; Wan, Jun; Chen, Jiwang; Smith, Kimberly A.; Fraidenburg, Dustin R.; Choudhury, Moumita S. R.; Levitan, Irena; Machado, Roberto F.; Kaplan, Jack H.; Yuan, Jason X.-J.

    2014-01-01

    Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu) plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX), a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2) also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC). In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α) with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness. PMID:24614111

  12. The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

    PubMed

    Smerup, Morten; Damkjær, Mads; Brøndum, Emil; Baandrup, Ulrik T; Kristiansen, Steen Buus; Nygaard, Hans; Funder, Jonas; Aalkjær, Christian; Sauer, Cathrine; Buchanan, Rasmus; Bertelsen, Mads Frost; Østergaard, Kristine; Grøndahl, Carsten; Candy, Geoffrey; Hasenkam, J Michael; Secher, Niels H; Bie, Peter; Wang, Tobias

    2016-02-01

    Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output. PMID:26643090

  13. Renin in differential diagnosis of hypertension.

    NASA Technical Reports Server (NTRS)

    Oparil, S.; Haber, E.

    1971-01-01

    Renin is a proteolytic enzyme secreted by the kidney. Techniques for the direct measurement of renin content of human blood are not available at the present time. Two of the best known causes of remediable hypertension can be diagnosed from abnormalities in renin activity and aldosterone production. In renovascular hypertension, renin secretion is increased because of impaired glomerular perfusion. The renin activity assay, when applied in a carefully controlled fashion, is a useful screening test for treatable causes of hypertension.

  14. Hypertension in Cardiovascular and Kidney Disease

    PubMed Central

    Botdorf, Joshua; Chaudhary, Kunal; Whaley-Connell, Adam

    2011-01-01

    The relationship between hypertension and chronic kidney disease (CKD) is bidirectional in nature and, generally, management strategies for cardiovascular risk reduction also attenuate progression of CKD. Prevalent hypertension increases with diminishing kidney function, and the management strategy changes with level of kidney function. In this review, we will examine the evidence for management of hypertension, as a modifiable risk factor for cardiovascular disease in CKD, and the impact of this management on progression of CKD. PMID:22096454

  15. Assessment of antioxidant enzyme activities in erythrocytes of pre-hypertensive and hypertensive women

    PubMed Central

    Amirkhizi, Farshad; Siassi, Fereydoun; Djalali, Mahmoud; Foroushani, Abbas Rahimi

    2010-01-01

    BACKGROUND: Few studies that have investigated hypertension have considered a state of oxidative stress that can contribute to the development of atherosclerosis and other hypertension induced organ damage. The aim of this study was to investigate whether pre-hypertension and hypertension status is associated with activities of erythrocyte antioxidant enzymes in a random sample of cardiovascular disease-free women. METHODS: In this case-control study, 53 pre-hypertensive women, 32 hypertensive women and 75 healthy controls were included. General information was gathered using questionnaires and face-to-face interviews. Blood pressure and anthropometric measurements were measured for each subject. Venous blood samples were drawn from subjects and plasma was separated. Activities of erythrocyte antioxidant enzymes were also evaluated by measuring activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT) in selected subjects. RESULTS: Fifty-three (33.1%) and 32 (20%) participants were pre-hypertensive and hypertensive, respectively. The hypertensive and pre-hypertensive women had lower CuZn-SOD (p < 0.001) and GPX (p < 0.01) activities compared to normotensives. Furthermore, hypertensive women had lower CAT activity compared to pre-hypertensive and normotensive women (p < 0.001). Moreover, significant differences were also observed between hypertensive and pre-hypertensive women in erythrocyte CAT activity (p < 0.01). CONCLUSIONS: The present findings show that activities of erythrocyte antioxidant enzymes decrease in pre-hypertensive and hypertensive women, which may eventually lead to atherosclerosis and other high blood pressure related health problems. PMID:21526095

  16. Hypertensive vascular remodeling was inhibited by Xuezhikang through the regulation of Fibulin-3 and MMPs in spontaneously hypertensive rats

    PubMed Central

    Lin, Zhong-Wei; Wang, Zhuo; Zhu, Gui-Ping; Li, Bo-Wei; Xie, Wen-Lin; Xiang, Ding-Cheng

    2015-01-01

    Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in vessels. In hypertension, extracellular matrix, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles in cardiovascular remodeling. However, the role of Fibulin-3 as an extracellular glycoprotein in hypertensive vascular remodeling remains unclear. Our study was to determine whether Fibulin-3 and TIMPs/MMPs would affect vascular structure during hypertension and the treatment of Xuezhikang. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomized to three groups: SHRs control group (SHRs group, n=10), group treated with low dose Xuezhikang (XZK-L, 20 mg/kg/d, n=10) and group treated with high dose Xuezhikang (XZK-H, 200 mg/kg/d, n=10), the normal group was comprised of ten Wistar-Kyoto (WKY) rats of the same age. We showed that serum nitric oxide (NO) in control group was significantly lower than WKY group (P<0.05). Concomitantly, serum oxidized low-density lipoprotein (ox-LDL) was higher than WKY group (P<0.05). The treatment of high dose Xuezhikang significantly dicreased ox-LDL, left ventricular mass index (LVMI) and Wall-to-lumen area ratio (W/L) of thoracic aorta (P<0.05), while serum NO was significantly increasing (P<0.05). Moreover, the expressions of Fibulin-3 and MMP-2, 9 at both protein and mRNA levels were significantly higher in thoracic aorta of SHRs group compared to WKY group by immunohistochemistry and western blotting (P<0.05). However, the levels of Fibulin-3 and MMP-2, 9 were significantly decreased in XZK-H group compared to control group (P<0.05). The level of TIMP-3 had no significance difference between SHRs and WKY groups (P>0.05). So the levels of Fibulin-3 and MMP-2, 9 in SHRs could be inhibited by Xuezhikang. Furthermore, a strong correlation in transcript expression was established between Fibulin-3, and MMP-2 (r=0.81, P<0.05) and MMP-9 (r=0.92, P<0.05) through immunohistochemistry. In

  17. Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension.

    PubMed

    Liu, Xin; Hu, Cheng; Bao, Minghui; Li, Jing; Liu, Xiaoyan; Tan, Xuerui; Zhou, Yong; Chen, Yequn; Wu, Shouling; Chen, Shuohua; Zhang, Rong; Jiang, Feng; Jia, Weiping; Wang, Xingyu; Yang, Xinchun; Cai, Jun

    2016-01-01

    Hypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10(-9); LOC729251, and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-β binding protein 1 (LTBP1), and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention. PMID:27480026

  18. Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension

    PubMed Central

    Liu, Xin; Hu, Cheng; Bao, Minghui; Li, Jing; Liu, Xiaoyan; Tan, Xuerui; Zhou, Yong; Chen, Yequn; Wu, Shouling; Chen, Shuohua; Zhang, Rong; Jiang, Feng; Jia, Weiping; Wang, Xingyu; Yang, Xinchun; Cai, Jun

    2016-01-01

    Hypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10−9; LOC729251, and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-β binding protein 1 (LTBP1), and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention. PMID:27480026

  19. Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling

    PubMed Central

    Luo, Wei-min; Kong, Jing; Gong, Yan; Liu, Xiao-qiong; Yang, Rui-xue; Zhao, Yu-xia

    2015-01-01

    Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of Fox

  20. Evidence-Based Chinese Medicine for Hypertension

    PubMed Central

    Wang, Jie; Xiong, Xingjiang

    2013-01-01

    Hypertension is an important worldwide public -health challenge with high mortality and disability. Due to the limitations and concerns with current available hypertension treatments, many hypertensive patients, especially in Asia, have turned to Chinese medicine (CM). Although hypertension is not a CM term, physicians who practice CM in China attempt to treat the disease using CM principles. A variety of approaches for treating hypertension have been taken in CM. For seeking the best evidence of CM in making decisions for hypertensive patients, a number of clinical studies have been conducted in China, which has paved the evidence-based way. After literature searching and analyzing, it appeared that CM was effective for hypertension in clinical use, such as Chinese herbal medicine, acupuncture, moxibustion, cupping, qigong, and Tai Chi. However, due to the poor quality of primary studies, clinical evidence is still weak. The potential benefits and safety of CM for hypertension still need to be confirmed in the future with well-designed RCTs of more persuasive primary endpoints and high-quality SRs. Evidence-based Chinese medicine for hypertension still has a long way to go. PMID:23861720

  1. Treatment of hypertension in the emergency department.

    PubMed

    Baumann, Brigitte M; Cline, David M; Pimenta, Eduardo

    2011-01-01

    This review updates concepts of hypertension evaluation and management in patients presenting to the emergency department. It outlines the current challenges faced by emergency physicians in the identification and management of hypertensive patients: In spite of published emergency care guidelines, identification and referral rates remain low in patients presenting to the emergency department with moderate blood pressure (BP) elevations. In patients with severely elevated BP, the evaluation for acute end organ damage remains inconsistent and is symptom-based. Using current consensus guidelines, this review provides an algorithm for the management of the hypertensive emergency department patient. The final section of this review outlines management strategies for specific hypertensive emergencies. PMID:21719370

  2. Evidence-based chinese medicine for hypertension.

    PubMed

    Wang, Jie; Xiong, Xingjiang

    2013-01-01

    Hypertension is an important worldwide public -health challenge with high mortality and disability. Due to the limitations and concerns with current available hypertension treatments, many hypertensive patients, especially in Asia, have turned to Chinese medicine (CM). Although hypertension is not a CM term, physicians who practice CM in China attempt to treat the disease using CM principles. A variety of approaches for treating hypertension have been taken in CM. For seeking the best evidence of CM in making decisions for hypertensive patients, a number of clinical studies have been conducted in China, which has paved the evidence-based way. After literature searching and analyzing, it appeared that CM was effective for hypertension in clinical use, such as Chinese herbal medicine, acupuncture, moxibustion, cupping, qigong, and Tai Chi. However, due to the poor quality of primary studies, clinical evidence is still weak. The potential benefits and safety of CM for hypertension still need to be confirmed in the future with well-designed RCTs of more persuasive primary endpoints and high-quality SRs. Evidence-based Chinese medicine for hypertension still has a long way to go. PMID:23861720

  3. Contrast stress echocardiography in hypertensive heart disease

    PubMed Central

    2011-01-01

    Hypertension is associated with atherosclerosis and cardiac and vascular structural and functional changes. Myocardial ischemia may arise in hypertension independent of coronary artery disease through an interaction between several pathophysiological mechanisms, including left ventricular hypertrophy, increased arterial stiffness and reduced coronary flow reserve associated with microvascular disease and endothelial dysfunction. The present case report demonstrates how contrast stress echocardiography can be used to diagnose myocardial ischemia in a hypertensive patient with angina pectoris but without significant obstructive coronary artery disease. The myocardial ischemia was due to severe resistant hypertension complicated with concentric left ventricular hypertrophy and increased arterial stiffness. PMID:22093163

  4. Dental management of patients with hypertension.

    PubMed

    Bavitz, J Bruce

    2006-10-01

    About 50 million people in the United States have hypertension. Many epidemiologists feels it is the number one public health problem in developed countries. Although asymptomatic early on, untreated hypertension leads to cardiovascular disease, strokes, renal failure, and blindness. Dentists no doubt treat patients with hypertension and its sequelae in their practice. This article summarizes the current thinking on the diagnosis and treatment of this condition, emphasizing dental implications. The article presents common oral and systemic side effects of antihypertensive medications, and discusses how dentists can help treat hypertension through the fabrication of devices useful in reducing obstructive sleep apnea. PMID:17000273

  5. Nerve conduction velocity in hypertensive patients.

    PubMed

    Halar, E M; Stewart, D T; Venkatesh, B; Chrissian, S A

    1978-01-01

    Due to conflicting reports in the literature regarding nerve conduction velocities (NCVs) in hypertensives, peroneal and sural NCVs and facial nerve conduction latencies were studied in 30 hypertensives and in 30 controls. An improved technique of NCV measurement was used. Twenty-one of the hypertensives were retested after five weeks, and five of them were tested for motor and sensory NCVs of the median nerve during a short period of partial occlusion of blood flow in the arm. No changes were found that could be related to blood pressure, duration of hypertension, eyeground changes, or partial restriction of blood flow. PMID:619818

  6. Hypertension crisis in the emergency department.

    PubMed

    Johnson, Wallace; Nguyen, My-Le; Patel, Ronak

    2012-11-01

    Hypertensive crises, which include hypertensive emergencies and urgencies, are frequently encountered in the emergency department, and require immediate attention as they can lead to irreversible end-organ damage. Normal blood pressure (BP) regulation is altered during acute rises in BP, leading to end-organ damage. Multiple organs can be injured. Special considerations should be given to hypertensive pregnant patients and patients with postoperative hypertension. Treatment should be individualized to each patient based on the type and extent of end-organ damage, degree of BP elevation, and the specific side effects that each medication could have on a patient's preexisting comorbidities. PMID:23102030

  7. Symmorphosis through Dietary Regulation: A Combinatorial Role for Proteolysis, Autophagy and Protein Synthesis in Normalising Muscle Metabolism and Function of Hypertrophic Mice after Acute Starvation

    PubMed Central

    Giallourou, Natasa; Matsakas, Antonios; Mitchell, Robert; Mararenkova, Helen; Flasskamp, Hannah; Macharia, Raymond; Ray, Steve; Swann, Jonathan R.; Sandri, Marco; Patel, Ketan

    2015-01-01

    Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production. PMID:25807490

  8. Monitoring and normalising a lack of appetite and weight loss. A discursive analysis of an online support group for bariatric surgery.

    PubMed

    Cranwell, Jo; Seymour-Smith, Sarah

    2012-06-01

    A significant adjustment in eating practices is required before and after bariatric surgery, yet we know relatively little about how patients manage these changes. In this paper, we explored how members of an online bariatric support group constructed their appetite and weight loss. Two hundred and eighty four online posts were collected, covering a period of just over a year, and analysed using discursive psychology. We found that a lack of appetite post-surgery was oriented to as something that was positively evaluated yet a cause for concern. Indeed, members monitored their food intake and marked out food consumption as a necessary activity in line with notions of healthy eating. Through monitoring members also normalised periods of weight stabilisation and were inducted into a group philosophy which encouraged a more holistic approach to post-surgery 'success'. Our analysis also highlights how monitoring and policing work as social support mechanisms which help to maintain weight management. Thus we argue, in line with others, that weight management, typically depicted as an individual responsibility, is bound up with the social practices of the online support group. We suggest that clinical advice about a loss of appetite and periods of weight stabilisation post-surgery perhaps need further explanation to patients. PMID:22342357

  9. The movement advantage in famous and unfamiliar faces: a comparison of point-light displays and shape-normalised avatar stimuli.

    PubMed

    Bennetts, Rachel J; Kim, Jeesun; Burke, Darren; Brooks, Kevin R; Lucey, Simon; Saragih, Jason; Robbins, Rachel A

    2013-01-01

    Facial movement may provide cues to identity, by supporting the extraction of face shape information via structure-from-motion, or via characteristic patterns of movement. Currently, it is unclear whether familiar and unfamiliar faces derive the same benefit from these mechanisms. This study examined the movement advantage by asking participants to match moving and static images of famous and unfamiliar faces to facial point-light displays (PLDs) or shape-normalised avatars in a same/different task (experiment 1). In experiment 2 we also used a same/different task, but participants matched from PLD to PLD or from avatar to avatar. In both experiments, unfamiliar face matching was more accurate for PLDs than for avatars, but there was no effect of stimulus type on famous faces. In experiment 1, there was no movement advantage, but in experiment 2, there was a significant movement advantage for famous and unfamiliar faces. There was no evidence that familiarity increased the movement advantage. For unfamiliar faces, results suggest that participants were relying on characteristic movement patterns to match the faces, and did not derive any extra benefit from the structure-from-motion cues in the PLDs. The results indicate that participants may use static and movement-based cues in a flexible manner when matching famous and unfamiliar faces. PMID:24386715

  10. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

    PubMed Central

    Neves, Rodrigo Vanerson Passos; Souza, Michel Kendy; Passos, Clévia Santos; Bacurau, Reury Frank Pereira; Simoes, Herbert Gustavo; Prestes, Jonato; Boim, Mirian Aparecida; Câmara, Niels Olsen Saraiva; Franco, Maria do Carmo Pinho; Moraes, Milton Rocha

    2016-01-01

    Background Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods Fifteen male SHR [206 ± 10 mmHg of systolic BP (SBP)] and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength. PMID:26840054

  11. Genetic implication of a novel thiamine transporter in human hypertension

    PubMed Central

    Zhang, Kuixing; Huentelman, Matthew J.; Rao, Fangwen; Sun, Eric I.; Corneveaux, Jason J.; Schork, Andrew J.; Wei, Zhiyun; Waalen, Jill; Miramontes-Gonzalez, Jose Pablo; Hightower, C. Makena; Maihofer, Adam X.; Mahata, Manjula; Pastinen, Tomi; Ehret, Georg B.; Schork, Nicholas J.; Eskin, Eleazar; Nievergelt, Caroline M.; Saier, Milton H.; O'Connor, Daniel T.

    2014-01-01

    Objectives We coupled two strategies – trait extremes and genome-wide pooling – to discover a novel BP locus that encodes a previously uncharacterized thiamine transporter. Background Hypertension is a heritable trait that remains the most potent and widespread cardiovascular risk factor, though details of its genetic determination are poorly understood. Methods Representative genomic DNA pools were created from male and female subjects in the highest and lowest 5th %iles of BP in a primary care population of >50,000 individuals. The peak associated SNPs were typed in individual DNA samples, as well as twins/siblings phenotyped for cardiovascular and autonomic traits. Biochemical properties of the associated transporter were evaluated in cellular assays. Results After chip hybridization and calculation of relative allele scores, the peak associations were typed in individual samples, revealing association of hypertension, SBP, and DBP to the previously uncharacterized solute carrier SLC35F3. The BP genetic association at SLC35F3 was validated by meta-analysis in an independent sample from the original source population, as well as the ICBP (across North America and Western Europe). Sequence homology to a putative yeast thiamine (vitamin B1) transporter prompted us to express human SLC35F3 in E. coli, which catalyzed [3H]-thiamine uptake. SLC35F3 risk allele (T/T) homozygotes displayed decreased erythrocyte thiamine content on microbiological assay. In twin pairs, the SLC35F3 risk allele predicted heritable cardiovascular traits previously associated with thiamine deficiency, including elevated cardiac stroke volume with decreased vascular resistance, and elevated pressor responses to environmental (cold) stress. Allelic expression imbalance (AEI) confirmed that cis-variation at the human SLC35F3 locus influenced expression of that gene, and the AEI peak coincided with the hypertension peak. Conclusions Novel strategies were coupled to position a new

  12. Identification of Stably Expressed lncRNAs as Valid Endogenous Controls for Profiling of Human Glioma

    PubMed Central

    Kraus, Theo F. J.; Greiner, Andrea; Guibourt, Virginie; Lisec, Kristina; Kretzschmar, Hans A.

    2015-01-01

    Background: Recent research indicates that long non-coding RNAs (lncRNA) represent a new family of RNAs that is of fundamental importance for controlling transcription and translation. Thereby, there is increasing evidence that lncRNAs are also important in tumourigenesis. Thereby valid expression profiling using quantitative PCR requires suitable, stably expressed normalisers to achieve reliable and reproducible data. However, no systematic analysis of suitable references in lncRNA studies in human glioma has been performed yet. Methods: In this study, we investigated 90 lncRNAs in 30 tissue specimen for the expression stability in human diffuse astrocytoma (WHO-Grade II), anaplastic astrocytoma (WHO-Grade III) and glioblastoma (WHO-Grade IV) both alone as well as in comparison with normal white matter. Our identification procedure included a rigorous bioinformatical selection process that resulted in the inclusion of only highly abundant, equally expressed lncRNAs for further analysis. Additionally, lncRNAs were classified according to their stability value using the NormFinder algorithm. Results: We identified 24 appropriate normalisers suitable for studies in diffuse astrocytoma, 22 for studies in anaplastic astrocytoma and 12 for studies in glioblastoma. Comparing all three glioma entities 7 lncRNAs showed stable expression levels. Addition of normal brain tissue resulted in only 4 suitable lncRNAs. Conclusions: Our findings indicate that 4 lncRNAs (HOXA6as, H19 upstream conserved 1 and 2, Zfhx2as and BC200) are suitable as normalisers in glioma and normal brain. These lncRNAs may thus be regarded as universal references being applicable for the accurate normalisation of lncRNA expression profiling in various glioma (WHO-Grades II-IV) alone and in combination with brain tissue. This enables to perform valid longitudinal studies, e.g. of glioma before and after malignisation to identify changes of lncRNA expressions probably driving malignant transformation

  13. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, and Assessment of Risk of Pediatric Hypertension.

    PubMed

    Harris, Kevin C; Benoit, Geneviève; Dionne, Janis; Feber, Janusz; Cloutier, Lyne; Zarnke, Kelly B; Padwal, Raj S; Rabi, Doreen M; Fournier, Anne

    2016-05-01

    We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented. These are categorized in a fashion similar to that of the existing adult recommendations. Specifically, we present recommendations on (1) accurate measurement of blood pressure in children, (2) criteria for diagnosis of hypertension in children, (3) assessment of overall cardiovascular risk in hypertensive children, (4) routine laboratory tests for the investigation of children with hypertension, (5) ambulatory blood pressure measurement in children, and (6) the role of echocardiography. We discuss the rationale for the recommendations and present additional supporting material for the clinician, including tables with standardized techniques for blood pressure measurement and determination of normative blood pressure values for children. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will update the recommendations annually and develop future evidence-based recommendations to guide prevention and treatment of pediatric hypertension. PMID:27118292

  14. Beta3 adrenergic receptor is involved in vascular injury in deoxycorticosterone acetate-salt hypertensive mice.

    PubMed

    Sheng, Li-Juan; Ruan, Cheng-Chao; Ma, Yu; Chen, Dong-Rui; Kong, Ling-Ran; Zhu, Ding-Liang; Gao, Ping-Jin

    2016-03-01

    Beta3 adrenergic receptor (ADRB3) mediates vessel relaxation in the endothelium while it modulates lipolysis in the adipose tissue. However, the function and regulation mechanism of ADRB3 in the perivascular adipose tissue (PVAT), especially in hypertension, is still unclear. We show that ADRB3 protein is upregulated in the PVAT of deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice, with the characteristics of PVAT browning and increased uncoupling protein 1 (UCP1) expression. Inhibition of ADRB3 with selective antagonist SR59230A caused serious vascular injury in vivo, even though UCP1 expression was downregulated. ADRB3 protein was regulated by let-7b, which was decreased in the PVAT of the DOCA-salt group. These data reveal that ADRB3 in PVAT contributes to vascular function in the progression of hypertension. PMID:26910302

  15. Gestational hypertension and the developmental origins of cardiac hypertrophy and diastolic dysfunction.

    PubMed

    Armstrong, David W J; Tse, M Yat; Wong, Philip G; Ventura, Nicole M; Meens, Jalna A; Johri, Amer M; Matangi, Murray F; Pang, Stephen C

    2014-06-01

    The developmental origins of health and disease refer to the theory that adverse maternal environments influence fetal development and the risk of cardiovascular disease in adulthood. We used the chronically hypertensive atrial natriuretic peptide knockout (ANP-/-) mouse as a model of gestational hypertension, and attempted to determine the effect of gestational hypertension on left ventricular (LV) structure and function in adult offspring. We crossed normotensive ANP+/+ females with ANP-/- males (yielding ANP+/-(WT) offspring) and hypertensive ANP-/- females with ANP+/+ males (yielding ANP+/-(KO) offspring). Cardiac gene expression was measured using real-time quantitative PCR. Cardiac function was assessed using echocardiography. Daily injections of isoproterenol (ISO) were used to induce cardiac stress. Collagen deposition was assessed using picrosirius red staining. All mice were 10 weeks of age. Gestational hypertension resulted in significant LV hypertrophy in offspring, with no change in LV function. Treatment with ISO resulted in significant LV diastolic dysfunction with a restrictive filling pattern (increased E/A ratio and E/e') and interstitial myocardial fibrosis only in ANP+/-(KO) and not ANP+/-(WT) offspring. Gestational hypertension programs adverse LV structural and functional remodeling in offspring. These data suggest that adverse maternal environments may increase the risk of heart failure in offspring later in life. PMID:24718734

  16. p38 MAPK Inhibition Improves Synaptic Plasticity and Memory in Angiotensin II-dependent Hypertensive Mice.

    PubMed

    Dai, Hai-Long; Hu, Wei-Yuan; Jiang, Li-Hong; Li, Le; Gaung, Xue-Feng; Xiao, Zhi-Cheng

    2016-01-01

    The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. p38 MAPK pathway plays an important role in hypertensive target organ damage. Activated p38 MAPK was seen in AD brain tissue. In this study, we found that long-term potentiation (LTP) of hippocampal CA1 was decreased, the density of the dendritic spines on the CA1 pyramidal cells was reduced, the p-p38 protein expression in hippocampus was elevated, and cognitive function was impaired in angiotensin II-dependent hypertensive C57BL/6 mice. In vivo, using a p38 heterozygous knockdown mice (p38(KI/+)) model, we showed that knockdown of p38 MAPK in hippocampus leads to the improvement of cognitive function and hippocampal synaptic plasticity in angiotensin II-dependent p38(KI/+) hypertensive mice. In vitro, LTP was improved in hippocampal slices from C57BL/6 hypertensive mice by treatment with p38MAPK inhibitor SKF86002. Our data demonstrated that p38 MAPK may be a potential therapeutic target for hypertension-related cognitive dysfunction. PMID:27283322

  17. Transcriptome Analysis in Rat Kidneys: Importance of Genes Involved in Programmed Hypertension

    PubMed Central

    Tain, You-Lin; Huang, Li-Tung; Chan, Julie Y. H.; Lee, Chien-Te

    2015-01-01

    Suboptimal conditions in pregnancy can elicit long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether there are common genes and pathways in the kidney are responsible for generating programmed hypertension among three different models using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received dexamethasone (DEX, 0.1 mg/kg) from gestational day 16 to 22, 60% high-fructose (HF) diet, or NG-nitro-l-arginine-methyester (l-NAME, 60 mg/kg/day) to conduct DEX, HF, or l-NAME model respectively. All three models elicited programmed hypertension in adult male offspring. We observed five shared genes (Bcl6, Dmrtc1c, Egr1, Inmt, and Olr1668) among three different models. The identified differential genes (DEGs) that are related to regulation of blood pressure included Aqp2, Ptgs1, Eph2x, Hba-a2, Apln, Guca2b, Hmox1, and Npy. RNA-Seq identified genes in arachidonic acid metabolism are potentially gatekeeper genes contributing to programmed hypertension. In addition, HF and DEX increased expression and activity of soluble epoxide hydrolase (Ephx2 gene encoding protein). Conclusively, the DEGs in arachidonic acid metabolism are potentially gatekeeper genes in programmed hypertension. The roles of DEGs identified by the RNA-Seq in this study deserve further clarification, to develop the potential interventions in the prevention of programmed hypertension. PMID:25739086

  18. p38 MAPK Inhibition Improves Synaptic Plasticity and Memory in Angiotensin II-dependent Hypertensive Mice

    PubMed Central

    Dai, Hai-long; Hu, Wei-yuan; Jiang, Li-hong; Li, Le; Gaung, Xue-feng; Xiao, Zhi-cheng

    2016-01-01

    The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. p38 MAPK pathway plays an important role in hypertensive target organ damage. Activated p38 MAPK was seen in AD brain tissue. In this study, we found that long-term potentiation (LTP) of hippocampal CA1 was decreased, the density of the dendritic spines on the CA1 pyramidal cells was reduced, the p-p38 protein expression in hippocampus was elevated, and cognitive function was impaired in angiotensin II-dependent hypertensive C57BL/6 mice. In vivo, using a p38 heterozygous knockdown mice (p38KI/+) model, we showed that knockdown of p38 MAPK in hippocampus leads to the improvement of cognitive function and hippocampal synaptic plasticity in angiotensin II-dependent p38KI/+ hypertensive mice. In vitro, LTP was improved in hippocampal slices from C57BL/6 hypertensive mice by treatment with p38MAPK inhibitor SKF86002. Our data demonstrated that p38 MAPK may be a potential therapeutic target for hypertension-related cognitive dysfunction. PMID:27283322

  19. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

    PubMed Central

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  20. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats.

    PubMed

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  1. Hypertensive crisis during pregnancy and postpartum period.

    PubMed

    Too, Gloria T; Hill, James B

    2013-08-01

    Hypertension affects 10% of pregnancies, many with underlying chronic hypertension, and approximately 1-2% will undergo a hypertensive crisis at some point during their lives. Hypertensive crisis includes hypertensive urgency and emergency; the American College of Obstetricians and Gynecologists describes a hypertensive emergency in pregnancy as persistent (lasting 15 min or more), acute-onset, severe hypertension, defined as systolic BP greater than 160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia. Pregnancy may be complicated by hypertensive crisis, with lower blood pressure threshold for end-organ damage than non-pregnant patients. Maternal assessment should include a thorough history. Fetal assessment should include heart rate tracing, ultrasound for growth and amniotic assessment, and Doppler evaluation if growth restriction is suspected. Initial management of hypertensive emergency (systolic BP >160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia) generally includes the rapid reduction of blood pressure through the use of intravenous antihypertensive medications, with goal systolic blood pressure between 140 mmHg and 150 mmHg and diastolic pressure between 90 mmHg and 100 mmHg. First-line intravenous drugs include labetalol and hydralazine, but other agents may be used, including esmolol, nicardipine, nifedipine, and, as a last resort, sodium nitroprusside. Among patients with hypertensive urgency, slower blood pressure reduction can be provided with oral agents. The objective of this article is to review the current understanding, diagnosis, and management of hypertensive crisis during pregnancy and the postpartum period. PMID:23916027

  2. Clinical Outcome of Hypertensive Uveitis

    PubMed Central

    Lewkowicz, Deborah; Willermain, François; Relvas, Lia Judice; Makhoul, Dorine; Janssens, Sarah; Janssens, Xavier; Caspers, Laure

    2015-01-01

    Purpose. To review the clinical outcome of patients with hypertensive uveitis. Methods. Retrospective review of uveitis patients with elevated intraocular pressure (IOP) > 25 mmHg and >1-year follow-up. Data are uveitis type, etiology, viral (VU) and nonviral uveitis (NVU), IOP, and medical and/or surgical treatment. Results. In 61 patients, IOP values are first 32.9 mmHg (SD: 9.0), highest 36.6 mmHg (SD: 9.9), 3 months after the first episode 19.54 mmHg (SD: 9.16), and end of follow-up 15.5 mmHg (SD: 6.24). Patients with VU (n = 25) were older (50.6 y/35.7 y, p = 0.014) and had more unilateral disease (100%/72.22%  p = 0.004) than those with NVU (n = 36). Thirty patients (49.2%) had an elevated IOP before topical corticosteroid treatment. Patients with viral uveitis might have higher first elevated IOP (36.0/27.5 mmHg, p = 0,008) and maximal IOP (40.28/34.06 mmHg, p = 0.0148) but this was not significant when limited to the measurements before the use of topical corticosteroids (p = 0.260 and 0.160). Glaucoma occurred in 15 patients (24.59%) and was suspected in 11 (18.03%) without difference in viral and nonviral groups (p = 0.774). Conclusion. Patients with VU were older and had more unilateral hypertensive uveitis. Glaucoma frequently complicates hypertensive uveitis. Half of the patients had an elevated IOP before topical corticosteroid treatment. PMID:26504598

  3. Arrhythmias in pulmonary arterial hypertension.

    PubMed

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2012-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  4. Arrhythmias in Pulmonary Arterial Hypertension

    PubMed Central

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2013-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  5. Hypertension and a missing kidney

    PubMed Central

    Raina, Rupesh; Gulani, Vikas; Mehta, Lina; Jacobs, Gretta H.; Joyce, Kelly; Ponsky, Todd A.; Kenagy, David N.

    2012-01-01

    Standard initial assessment via ultrasound of a 4-year-old girl with hypertension revealed the absence of one kidney. Instead of cross-sectional imaging of the retroperitoneal space, a functional (nuclear) study was performed. This revealed a malformed kidney within the chest. Though systemic levels of renin and aldosterone were not elevated, removal of the malformed kidney normalized the blood pressure. The presence of prominent smooth muscle nodules surrounding the arteries was seen in the malformed kidney. Initial attempts to avert surgery by pharmacologically reducing blood flow to the malformed kidney were unsuccessful. The review of the literature offers little evidence to support such a strategy. PMID:25874090

  6. Post splenectomy related pulmonary hypertension

    PubMed Central

    Palkar, Atul V; Agrawal, Abhinav; Verma, Sameer; Iftikhar, Asma; Miller, Edmund J; Talwar, Arunabh

    2015-01-01

    Splenectomy predisposes patients to a slew of infectious and non-infectious complications including pulmonary vascular disease. Patients are at increased risk for venous thromboembolic events due to various mechanisms that may lead to chronic thromboembolic pulmonary hypertension (CTEPH). The development of CTEPH and pulmonary vasculopathy after splenectomy involves complex pathophysiologic mechanisms, some of which remain unclear. This review attempts congregate the current evidence behind our understanding about the etio-pathogenesis of pulmonary vascular disease related to splenectomy and highlight the controversies that surround its management. PMID:26949600

  7. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  8. Hypertension treatment in the Asia-Pacific: the role of and treatment strategies with nebivolol

    PubMed Central

    Kim, Cheol-Ho; Abelardo, Nelson; Buranakitjaroen, Peera; Krittayaphong, Rungroj; Lim, Chin Hock; Park, Sung-Ha; Pham, Nguyen Vinh; Rogelio, Gregorio; Wong, Bernard; Low, Lip Ping

    2016-01-01

    Hypertension is a common disease, and hypertensive patients are at increased risk of cardiovascular events. The prevalence and socioeconomic burden of hypertension in the Asia-Pacific region are predicted to increase in the coming decades. Effective blood pressure lowering reduces overall cardiovascular morbidity and mortality in patients, yet doubt has been raised regarding the use of (mainly older generation) β-blockers as initial therapy in hypertension. Consequently, several international treatment guidelines do not recommend β-blockers for the treatment of hypertension. However, in contrast to first-generation and second-generation β-blockers, the third-generation, vasodilating β-blocker nebivolol has a considerably better metabolic, haemodynamic and side effect profile. In addition to providing effective blood pressure control similar to other β-blockers and drugs from other antihypertensive classes, nebivolol exerts a dual mechanism for increasing the bioavailability of the naturally occurring vasodilator nitric oxide. The clinical benefits and significance of enhancing nitric oxide levels in hypertensive patients have been shown in direct comparisons of nebivolol with other β-blockers. While β-blockers generally provide comparable blood pressure reductions, only nebivolol demonstrated enhanced vasodilation and blood flow by increasing the expression of endothelial nitric oxide synthase and therefore increasing nitric oxide release from the endothelium. In contrast to other β-blockers, therefore, it has been suggested that nebivolol has beneficial effects in several hypertensive subgroups due to its vasodilating properties. Considering the existing data, it may be timely for treatment guidelines to recommend third-generation vasodilating β-blockers as a first-line option for the pharmacotherapy of hypertension. PMID:27326226

  9. Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).

    PubMed

    Furedi, Nora; Miko, Alexandra; Aubrecht, Bianka; Gaszner, Balazs; Feller, Diana; Rostas, Ildiko; Tenk, Judit; Soos, Szilvia; Balasko, Marta; Balogh, Andras; Pap, Marianna; Petervari, Erika

    2016-08-01

    Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR. PMID:27339773

  10. Extracorporeal shock wave therapy does not improve hypertensive nephropathy.

    PubMed

    Caron, Jonathan; Michel, Pierre-Antoine; Dussaule, Jean-Claude; Chatziantoniou, Christos; Ronco, Pierre; Boffa, Jean-Jacques

    2016-06-01

    Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF-R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated. PMID:27255359

  11. Portal hypertensive polyps, a new entity?

    PubMed

    Martín Domínguez, Verónica; Díaz Méndez, Ariel; Santander, Cecilio; García-Buey, Luisa

    2016-05-01

    We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP). PMID:27188590

  12. Mechanisms of obesity-induced hypertension.

    PubMed

    Kotsis, Vasilios; Stabouli, Stella; Papakatsika, Sofia; Rizos, Zoe; Parati, Gianfranco

    2010-05-01

    The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. PMID:20442753

  13. Pulmonary Hypertension in Pregnancy: Critical Care Management

    PubMed Central

    Bassily-Marcus, Adel M.; Yuan, Carol; Oropello, John; Manasia, Anthony; Kohli-Seth, Roopa; Benjamin, Ernest

    2012-01-01

    Pulmonary hypertension is common in critical care settings and in presence of right ventricular failure is challenging to manage. Pulmonary hypertension in pregnant patients carries a high mortality rates between 30–56%. In the past decade, new treatments for pulmonary hypertension have emerged. Their application in pregnant women with pulmonary hypertension may hold promise in reducing morbidity and mortality. Signs and symptoms of pulmonary hypertension are nonspecific in pregnant women. Imaging workup may have undesirable radiation exposure. Pulmonary artery catheter remains the gold standard for diagnosing pulmonary hypertension, although its use in the intensive care unit for other conditions has slowly fallen out of favor. Goal-directed bedside echocardiogram and lung ultrasonography provide attractive alternatives. Basic principles of managing pulmonary hypertension with right ventricular failure are maintaining right ventricular function and reducing pulmonary vascular resistance. Fluid resuscitation and various vasopressors are used with caution. Pulmonary-hypertension-targeted therapies have been utilized in pregnant women with understanding of their safety profile. Mainstay therapy for pulmonary embolism is anticoagulation, and the treatment for amniotic fluid embolism remains supportive care. Multidisciplinary team approach is crucial to achieving successful outcomes in these difficult cases. PMID:22848817

  14. Measuring hypertension control: NCQA and beyond.

    PubMed

    Miller, Nancy Houston

    2003-08-01

    Using tools developed by NCQA, Rand, and other institutions, health plans and providers can take an aggressive stance toward managing hypertension. This effort has led to gains in blood pressure control in some populations, greater recognition of the importance of controlling hypertension, and increased attention to processes that promote higher-quality health care. PMID:12971593

  15. Hypertension. Part 1: How Exercise Helps.

    ERIC Educational Resources Information Center

    Tanji, Jeffrey L.

    1990-01-01

    Reviews possible mechanisms by which exercise lowers blood pressure and discusses research which indicates exercise is an effective therapy for hypertension. The article presents information to help physicians counsel hypertensive patients wanting to start an exercise program and examines the use of exercise testing to predict the onset of…

  16. Pulmonary hypertension in pregnancy: critical care management.

    PubMed

    Bassily-Marcus, Adel M; Yuan, Carol; Oropello, John; Manasia, Anthony; Kohli-Seth, Roopa; Benjamin, Ernest

    2012-01-01

    Pulmonary hypertension is common in critical care settings and in presence of right ventricular failure is challenging to manage. Pulmonary hypertension in pregnant patients carries a high mortality rates between 30-56%. In the past decade, new treatments for pulmonary hypertension have emerged. Their application in pregnant women with pulmonary hypertension may hold promise in reducing morbidity and mortality. Signs and symptoms of pulmonary hypertension are nonspecific in pregnant women. Imaging workup may have undesirable radiation exposure. Pulmonary artery catheter remains the gold standard for diagnosing pulmonary hypertension, although its use in the intensive care unit for other conditions has slowly fallen out of favor. Goal-directed bedside echocardiogram and lung ultrasonography provide attractive alternatives. Basic principles of managing pulmonary hypertension with right ventricular failure are maintaining right ventricular function and reducing pulmonary vascular resistance. Fluid resuscitation and various vasopressors are used with caution. Pulmonary-hypertension-targeted therapies have been utilized in pregnant women with understanding of their safety profile. Mainstay therapy for pulmonary embolism is anticoagulation, and the treatment for amniotic fluid embolism remains supportive care. Multidisciplinary team approach is crucial to achieving successful outcomes in these difficult cases. PMID:22848817

  17. Minority Barbers Screen Customers for Hypertension.

    ERIC Educational Resources Information Center

    Pepe, Margaret V.

    1989-01-01

    Offering hypertension screening within the Black community in a convenient, nonthreatening environment can aid in reduction of morbidity and mortality attributable to high blood pressure in Black men. This article describes a successful pilot program which used volunteer barbers to perform on-site hypertension screening for their customers. (IAH)

  18. Lysine deacetylase inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptor instead of histone acetylation in spontaneously hypertensive rats.

    PubMed

    Seok, Young Mi; Lee, Hae Ahm; Park, Kwon Moo; Hwangbo, Mi-Hyang; Kim, In Kyeom

    2016-07-01

    Inhibition of lysine deacetylase (KDAC) attenuated development of hypertension in spontaneously hypertensive rats (SHRs). We hypothesized that KDAC inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptors (MR) instead of histone acetylation in SHRs. Valproate (VPA, 0.71 % wt/vol), an inhibitor of class I KDACs, was administered in drinking water to 7-week-old SHRs and Wistar Kyoto rats for 11 weeks. MR acetylation was determined by immunoprecipitation with anti-MR antibody followed by western blot with anti-acetyl-lysine antibody. Expression levels of acetylated histone H3, KDACs, MR target genes, or MR corepressors in the kidney cortex were measured by using western blot analysis or real-time PCR. Recruitment of MR and RNA polymerase II (Pol II) and histone modifications on promoters of target genes were analyzed by performing a chromatin immunoprecipitation (ChIP) assay. Treatment of SHR with VPA increased MR acetylation without affecting MR expression, which attenuated development of hypertension in SHR VPA decreased expression of KDAC class I but globally increased acetylated histone H3. Although VPA treatment increased histone 3 acetylation (H3Ac) and trimethylation of the fourth lysine (H3K4me3) in the promoter regions of MR target genes, it decreased the expression of target genes as well as recruitment of MR and Pol II. These results suggest that KDAC inhibition attenuates the development of hypertension in SHRs and is accompanied by acetylation of MR that is independent of histone acetylation. PMID:27106211

  19. The relationships of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease.

    PubMed

    Chang, Chih-Ping; Li, Tsai-Chung; Hang, Liang-Wen; Liang, Shinn-Jye; Lin, Jen-Jyn; Chou, Che-Yi; Tsai, Jeffrey J P; Ko, Po-Yen; Chang, Chiz-Tzung

    2016-06-01

    Hypertension, blood pressure variation, and resistant hypertension have close relations to sleep apnea, which lead to target organ damage, including the kidney. The complex relationships between sleep apnea and blood pressure cause their interactions with chronic kidney disease ambiguous. The aim of the study was to elucidate the separate and joint effects of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. A cross-sectional study was done to see the associations of sleep apnea, hypertension, and resistant hypertension with chronic kidney disease in 998 subjects underwent overnight polysomnography without device-therapy or surgery for their sleep-disordered breathing. Multivariate logistic regression was used to analyze the severity of SA, hypertension stage, resistant hypertension, and their joint effects on CKD. The multivariable relative odds (95% CI) of chronic kidney disease for the aged (age ≥65 years), severe sleep apnea, stage III hypertension, and resistant hypertension were 3.96 (2.57-6.09) (P < 0.001), 2.28 (1.13-4.58) (P < 0.05), 3.55 (1.70-7.42) (P < 0.001), and 9.42 (4.22-21.02) (P < 0.001), respectively. In subgroups analysis, the multivariable relative odds ratio of chronic kidney disease was highest in patients with both resistant hypertension and severe sleep apnea [13.42 (4.74-38.03)] (P < 0.001). Severe sleep apnea, stage III hypertension, and resistant hypertension are independent risk factors for chronic kidney disease. Patients with both severe sleep apnea and resistant hypertension have the highest risks. PMID:27281098

  20. The relationships of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease

    PubMed Central

    Chang, Chih-Ping; Li, Tsai-Chung; Hang, Liang-Wen; Liang, Shinn-Jye; Lin, Jen-Jyn; Chou, Che-Yi; Tsai, Jeffrey J.P.; Ko, Po-Yen; Chang, Chiz-Tzung

    2016-01-01

    Abstract Hypertension, blood pressure variation, and resistant hypertension have close relations to sleep apnea, which lead to target organ damage, including the kidney. The complex relationships between sleep apnea and blood pressure cause their interactions with chronic kidney disease ambiguous. The aim of the study was to elucidate the separate and joint effects of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. A cross-sectional study was done to see the associations of sleep apnea, hypertension, and resistant hypertension with chronic kidney disease in 998 subjects underwent overnight polysomnography without device-therapy or surgery for their sleep-disordered breathing. Multivariate logistic regression was used to analyze the severity of SA, hypertension stage, resistant hypertension, and their joint effects on CKD. The multivariable relative odds (95% CI) of chronic kidney disease for the aged (age ≥65 years), severe sleep apnea, stage III hypertension, and resistant hypertension were 3.96 (2.57–6.09) (P < 0.001), 2.28 (1.13–4.58) (P < 0.05), 3.55 (1.70–7.42) (P < 0.001), and 9.42 (4.22–21.02) (P < 0.001), respectively. In subgroups analysis, the multivariable relative odds ratio of chronic kidney disease was highest in patients with both resistant hypertension and severe sleep apnea [13.42 (4.74–38.03)] (P < 0.001). Severe sleep apnea, stage III hypertension, and resistant hypertension are independent risk factors for chronic kidney disease. Patients with both severe sleep apnea and resistant hypertension have the highest risks. PMID:27281098

  1. [Hypertension during pregnancy: the challenge continues].

    PubMed

    Rosas-Peralta, Martín; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto

    2016-01-01

    Hypertensive disorders of pregnancy affect approximately from 5 to 10 % of all pregnant women, and are the main contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, as well as the conditions that arise de novo in pregnancy: gestational hypertension and preeclampsia. This last group is believed to be part of the same continuum, but with arbitrary division. Research on the etiology of hypertension in pregnancy largely have focused on preeclampsia, with a majority of studies that explore any factor associated with pregnancy, e.g., the answers derived from the placenta or immunological reactions to tissue from the pregnancy or maternal constitutional factors, such as cardiovascular health and endothelial dysfunction. The basic foundations for the pathophysiology and progression of hypertensive pregnancy disorders, particularly preeclampsia, are reviewed in this paper. Therapeutic options for the treatment of preeclampsia are also explored. PMID:27284848

  2. [Radiographic assessment of pulmonary hypertension: Methodical aspects].

    PubMed

    Korobkova, I Z; Lazutkina, V K; Nizovtsova, L A; Riden, T V

    2015-01-01

    Pulmonary hypertension is a menacing complication of a number of diseases, which is responsible for high mortality rates and considerably poorer quality of life in a patient. The timely detection for pulmonary hypertension allows timely initiation of treatment, thus improvement in prognosis in the patient. Chest X-ray is the most commonly used radiographic technique for various causes. Physicians' awareness about the radiographic manifestations of pulmonary hypertension may contribute to the earlier detection of this severe disease. Owing to the natural contrast of reflected structures, a chest X-ray film gives a unique opportunity to assess pulmonary circulation vessels, to reveal the signs of pulmonary hypertension, and to estimate trends in the course of the disease. The paper details a procedure for analysis and the normal radiographic anatomy of pulmonary circulation vessels, gives the present classification of pulmonary hypertension, and sets forth its X-ray semiotics. PMID:26552229

  3. Hotel Housekeeping Work Influences on Hypertension Management

    PubMed Central

    Sanon, Marie-Anne

    2013-01-01

    Background Characteristics of hotel housekeeping work increase the risk for hypertension development. Little is known about the influences of such work on hypertension management. Methods For this qualitative study, 27 Haitian immigrant hotel housekeepers from Miami-Dade County, FL were interviewed. Interview transcripts were analyzed with the assistance of the Atlas. ti software for code and theme identification. Results Influences of hotel housekeeping work on hypertension management arose both at the individual and system levels. Factors at the individual level included co-worker dynamics and maintenance of transmigrant life. Factors at the system level included supervisory support, workload, work pace, and work hiring practices. No positive influences were reported for workload and hiring practices. Conclusions Workplace interventions may be beneficial for effective hypertension management among hotel housekeepers. These work influences must be considered when determining effective methods for hypertension management among hotel housekeepers. PMID:23775918

  4. With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies

    PubMed Central

    Chapman, Joanne R.; Waldenström, Jonas

    2015-01-01

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies. PMID:26555275

  5. Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension.

    PubMed

    Youn, Ji Youn; Wang, Ting; Blair, John; Laude, Karine M; Oak, Jeong-Ho; McCann, Louise A; Harrison, David G; Cai, Hua

    2012-06-01

    The endothelial nitric oxide synthase (eNOS) requires tetrahydrobiopterin (H(4)B) as a cofactor and, in its absence, produces superoxide (O(2)(·-)) rather than nitric oxide (NO(·)), a condition referred to as eNOS uncoupling. DOCA-salt-induced hypertension is associated with H(4)B oxidation and uncoupling of eNOS. The present study investigated whether administration of sepiapterin or H(4)B recouples eNOS in DOCA-salt hypertension. Bioavailable NO(·) detected by electron spin resonance was markedly reduced in aortas of DOCA-salt hypertensive mice. Preincubation with sepiapterin (10 μmol/l for 30 min) failed to improve NO(·) bioavailability in hypertensive aortas while it augmented NO(·) production from control vessels, implicating a hypertension-associated deficiency in sepiapterin reductase (SPR), the rate-limiting enzyme for sepiapterin conversion to H(4)B. Indeed, a decreased SPR expression was observed in aortic endothelial cells, but not in endothelium-denuded aortic remains, implicating an endothelium-specific SPR deficiency. Administration of hypertensive aortas with H(4)B (10 μmol/l, 30 min) partially restored vascular NO(·) production. Combined administration of H(4)B and the NADPH oxidase inhibitor apocynin (100 μmol/l, 30 min) fully restored NO(·) bioavailability while reducing O(2)(·-) production. In angiotensin II-induced hypertension, however, aortic endothelial SPR expression was not affected. In summary, administration of sepiapterin is not effective in recoupling eNOS in DOCA-salt hypertension, due to an endothelium-specific loss in SPR, whereas coadministration of H(4)B and apocynin is highly efficient in recoupling eNOS. This is consistent with our previous observations that in angiotensin II hypertension, endothelial deficiency in dihydrofolate reductase is alternatively responsible for uncoupling of eNOS. Taken together, these data indicate that strategies specifically targeting at different H(4)B metabolic enzymes might be necessary

  6. Sex-Dependent Influence of Endogenous Estrogen in Pulmonary Hypertension

    PubMed Central

    Mair, Kirsty M.; Wright, Audrey F.; Duggan, Nicholas; Rowlands, David J.; Hussey, Martin J.; Roberts, Sonia; Fullerton, Josephine; Nilsen, Margaret; Loughlin, Lynn; Thomas, Matthew

    2014-01-01

    Rationale: The incidence of pulmonary arterial hypertension is greater in women, suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males, exogenously administered estrogen can protect against pulmonary hypertension (PH). However, in models that display female susceptibility, estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and sex in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH: the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of sex on pulmonary expression of aromatase in these models and in lungs from patients with pulmonary arterial hypertension. Measurements and Main Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was caused by reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor α also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased bone morphogenetic protein receptor 2 and Id1 expression compared with male. Anastrozole treatment reversed the impaired bone morphogenetic protein receptor 2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared with male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential. PMID:24956156

  7. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

    PubMed

    Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

    2015-03-01

    The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. PMID:25547342

  8. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    PubMed

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers. PMID:23281754

  9. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.

    PubMed

    Martínez-Martínez, Ernesto; Calvier, Laurent; Fernández-Celis, Amaya; Rousseau, Elodie; Jurado-López, Raquel; Rossoni, Luciana V; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; Cachofeiro, Victoria; López-Andrés, Natalia

    2015-10-01

    Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension. PMID:26238446

  10. Hepatopulmonary syndrome and portopulmonary hypertension.

    PubMed

    Hendrickse, Adrian; Azam, Fareed; Mandell, M Susan

    2007-04-01

    The incidence of pulmonary vascular disorders is significantly increased in patients with liver disease. Intrapulmonary shunting with hypoxemia in patients with liver disease is diagnosed as hepatopulmonary syndrome (HPS), whereas precapillary pulmonary vessel obliteration is identified as portopulmonary hypertension (PPHTN). Because the symptoms of liver disease can mimic those of pulmonary vascular disease, all patients with hepatic failure should be screened for these two diseases. Pulse oximetry effectively screens for hypoxemia associated with HPS, whereas an elevated right ventricular systolic pressure estimated by echocardiography identifies patients at risk of having PPHTN. Liver transplantation is the only effective medical therapy for HPS. However, those who have a resting arterial oxygenation less than 50 mm Hg or a shunt measured by scintigraphic perfusion greater than 20% have an unacceptably high mortality rate following surgery. Compared with HPS, there are more therapeutic options that can bridge patients with PPHTN to transplantation. Drugs used to manage idiopathic pulmonary hypertension have shown promise in the treatment of PPHTN. Prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors have improved transplant survival. Despite treatment, however, perioperative mortality for patients with PPHTN remains high. Even with successful transplantation, HPS and PPHTN can persist or develop de novo. Long-term follow-up and surveillance of liver transplant recipients is thus indicated to identify HPS and PPHTN following surgery. PMID:17484815

  11. Virgin Olive Oil and Hypertension.

    PubMed

    Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Jaramillo, Sara; Abia, Rocio; Muriana, Francisco Jg

    2016-01-01

    The incidence of high blood pressure (BP) along with other cardiovascular (CV) risk factors on human health has been studied for many years. These studies have proven a link between unhealthy dietary habits and sedentary lifestyle with the onset of hypertension, which is a hallmark of CV and cerebrovascular diseases. The Mediterranean diet, declared by the UNESCO as an Intangible Cultural Heritage since 2013, is rich in vegetables, legumes, fruits and virgin olive oil. Thanks to its many beneficial effects, including those with regard to lowering BP, the Mediterranean diet may help people from modern countries to achieve a lower occurrence of CV disease. Data from human and animal studies have shown that the consumption of virgin olive oil shares most of the beneficial effects of the Mediterranean diet. Virgin olive oil is the only edible fat that can be consumed as a natural fruit product with no additives or preservatives, and contains a unique constellation of bioactive entities, namely oleic acid and minor constituents. In this review, we summarize what is known about the effects of virgin olive oil on hypertension. PMID:26775852

  12. REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

    PubMed Central

    Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

    2013-01-01

    Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies

  13. Adrenal dysfunction in portal hypertensive rats with acute hemorrhage.

    PubMed

    Lee, Fa-Yauh; Wang, Sun-Sang; Tsai, Ming-Hung; Huang, Hui-Chun; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the 'hepatoadrenal syndrome', but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  14. Adrenal Dysfunction in Portal Hypertensive Rats with Acute Hemorrhage

    PubMed Central

    Lee, Fa-Yauh; Wang, Sun-Sang; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the ‘hepatoadrenal syndrome’, but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  15. Evaluation of the serotonin receptor blockers ketanserin and methiothepin on the pulmonary hypertensive responses of broilers to intravenously infused serotonin.

    PubMed

    Chapman, M E; Wideman, R F

    2006-04-01

    The pathogenesis of pulmonary hypertension remains incompletely understood. Many factors have been implicated; however, there has been great interest in the potent pulmonary vasoconstrictor serotonin (5-HT) due to episodes of primary pulmonary hypertension in humans triggered by serotoninergic appetite-suppressant drugs. Pulmonary hypertensive patients have elevated blood 5-HT levels and pulmonary vasoconstriction induced by 5-HT is believed to be mediated through 5-HT1B/1D and 5-HT2A receptors that are expressed by pulmonary smooth muscle cells. The vascular remodeling associated with pulmonary hypertension also appears to require the serotonin transporter. We investigated the roles of 5-HT receptor blockers on the development of pulmonary hypertension induced by infusing 5-HT i.v. in broilers. For this purpose, we treated broilers with the selective 5-HT2A receptor antagonist ketanserin (5 mg/ kg of BW) or with the nonselective 5-HT1/2 receptor antagonist methiothepin (3 mg/kg of BW). Receptor blockade was followed by infusion of 5-HT while recording pulmonary arterial pressure and pulmonary arterial blood flow. The results demonstrate that methiothepin, but not ketanserin, eliminated the 5-HT-induced pulmonary hypertensive responses in broilers. The 5-HT2A receptor does not, therefore, appear to play a role in the 5-HT-induced pulmonary hypertensive responses in broilers. Methiothepin did not inhibit pulmonary vascular contractility per se, because the pulmonary hypertensive response to the thromboxane A2 mimetic U44069 remained intact in methiothepin-treated broilers. Methiothepin will be a useful tool for evaluating the role of 5-HT in the pathogenesis of pulmonary hypertension syndrome (ascites) as well as the onset of pulmonary hypertension triggered by inflammatory stimuli such as bacterial lipolysaccharide. PMID:16615363

  16. Eliciting symptoms interpreted as normal by patients with early-stage lung cancer: could GP elicitation of normalised symptoms reduce delay in diagnosis? Cross-sectional interview study

    PubMed Central

    Brindle, Lucy; Pope, Catherine; Corner, Jessica; Leydon, Geraldine; Banerjee, Anindo

    2012-01-01

    Objectives To investigate why symptoms indicative of early-stage lung cancer (LC) were not presented to general practitioners (GPs) and how early symptoms might be better elicited within primary care. Design, setting and participants A qualitative cross-sectional interview study about symptoms and help-seeking in 20 patients from three south England counties, awaiting resection of LC (suspected or histologically confirmed). Analysis drew on principles of discourse analysis and constant comparison to identify processes involved in interpretation and communication about symptoms, and explain non-presentation. Results Most participants experienced health changes possibly indicative of LC which had not been presented during GP consultations. Symptoms that were episodic, or potentially caused by ageing or lifestyle, were frequently not presented to GPs. In interviews, open questions about health changes/symptoms in general did not elicit these symptoms; they only emerged in response to closed questions detailing specific changes in health. Questions using disease-related labels, for example, pain or breathlessness, were less likely to elicit symptoms than questions that used non-disease terminology, such as aches, discomfort or ‘getting out of breath’. Most participants described themselves as feeling well and were reluctant to associate potentially explained, non-specific or episodic symptoms with LC, even after diagnosis. Conclusions Patients with early LC are unlikely to present symptoms possibly indicative of LC that they associate with normal processes, when attending primary care before diagnosis. Faced with patients at high LC risk, GPs will need to actively elicit potential LC symptoms not presented by the patient. Closed questions using non-disease terminology might better elicit normalised symptoms. PMID:23166137

  17. Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

    PubMed

    Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

    2014-06-01

    A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. PMID:24785760

  18. Dietary chia seed (Salvia hispanica L.) rich in alpha-linolenic acid improves adiposity and normalises hypertriacylglycerolaemia and insulin resistance in dyslipaemic rats.

    PubMed

    Chicco, Adriana G; D'Alessandro, Maria E; Hein, Gustavo J; Oliva, Maria E; Lombardo, Yolanda B

    2009-01-01

    The present study investigates the benefits of the dietary intake of chia seed (Salvia hispanica L.) rich in alpha-linolenic acid and fibre upon dyslipidaemia and insulin resistance (IR), induced by intake of a sucrose-rich (62.5 %) diet (SRD). To achieve these goals two sets of experiments were designed: (i) to study the prevention of onset of dyslipidaemia and IR in Wistar rats fed during 3 weeks with a SRD in which chia seed was the dietary source of fat; (ii) to analyse the effectiveness of chia seed in improving or reversing the metabolic abnormalities described above. Rats were fed a SRD during 3 months; by the end of this period, stable dyslipidaemia and IR were present in the animals. From months 3-5, half the animals continued with the SRD and the other half were fed a SRD in which the source of fat was substituted by chia seed (SRD+chia). The control group received a diet in which sucrose was replaced by maize starch. The results showed that: (i) dietary chia seed prevented the onset of dyslipidaemia and IR in the rats fed the SRD for 3 weeks--glycaemia did not change; (ii) dyslipidaemia and IR in the long-term SRD-fed rats were normalised without changes in insulinaemia when chia seed provided the dietary fat during the last 2 months of the feeding period. Dietary chia seed reduced the visceral adiposity present in the SRD rats. The present study provides new data regarding the beneficial effect of chia seed upon lipid and glucose homeostasis in an experimental model of dislipidaemia and IR. PMID:18492301

  19. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

    PubMed

    Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

    2001-08-01

    Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats. PMID:11509478

  20. Medical therapies for pulmonary arterial hypertension.

    PubMed

    Pulido, Tomas; Zayas, Nayeli; de Mendieta, Maitane Alonso; Plascencia, Karen; Escobar, Jennifer

    2016-05-01

    Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure. PMID:26791159

  1. Hypertension

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  2. Masked Hypertension and Incident Clinic Hypertension Among Blacks in the Jackson Heart Study.

    PubMed

    Abdalla, Marwah; Booth, John N; Seals, Samantha R; Spruill, Tanya M; Viera, Anthony J; Diaz, Keith M; Sims, Mario; Muntner, Paul; Shimbo, Daichi

    2016-07-01

    Masked hypertension, defined as nonelevated clinic blood pressure (BP) and elevated out-of-clinic BP may be an intermediary stage in the progression from normotension to hypertension. We examined the associations of out-of-clinic BP and masked hypertension using ambulatory BP monitoring with incident clinic hypertension in the Jackson Heart Study, a prospective cohort of blacks. Analyses included 317 participants with clinic BP <140/90 mm Hg, complete ambulatory BP monitoring, who were not taking antihypertensive medication at baseline in 2000 to 2004. Masked daytime hypertension was defined as mean daytime blood pressure ≥135/85 mm Hg, masked night-time hypertension as mean night-time BP ≥120/70 mm Hg, and masked 24-hour hypertension as mean 24-hour BP ≥130/80 mm Hg. Incident clinic hypertension, assessed at study visits in 2005 to 2008 and 2009 to 2012, was defined as the first visit with clinic systolic/diastolic BP ≥140/90 mm Hg or antihypertensive medication use. During a median follow-up of 8.1 years, there were 187 (59.0%) incident cases of clinic hypertension. Clinic hypertension developed in 79.2% and 42.2% of participants with and without any masked hypertension, 85.7% and 50.4% with and without masked daytime hypertension, 79.9% and 43.7% with and without masked night-time hypertension, and 85.7% and 48.2% with and without masked 24-hour hypertension, respectively. Multivariable-adjusted hazard ratios (95% confidence interval) of incident clinic hypertension for any masked hypertension and masked daytime, night-time, and 24-hour hypertension were 2.13 (1.51-3.02), 1.79 (1.24-2.60), 2.22 (1.58-3.12), and 1.91 (1.32-2.75), respectively. These findings suggest that ambulatory BP monitoring can identify blacks at increased risk for developing clinic hypertension. PMID:27185746

  3. Anti-hypertensive property of a nickel-piperazine/NO donor in spontaneously hypertensive rats.

    PubMed

    Monti, Martina; Ciccone, Valerio; Pacini, Aurora; Roggeri, Riccardo; Monzani, Enrico; Casella, Luigi; Morbidelli, Lucia

    2016-05-01

    The nickel-piperazine/NO donor compound, Ni(PipNONO)Cl, belonging to the family of compounds labelled as "metal-nonoates", due to its promising vasodilating activity, has been considered as a potential drug candidate in anti-hypertensive therapy. Drug efficacy has been evaluated in spontaneously hypertensive rats (SHR) in comparison with normotensive animals (C57BL/6 mice and WKY rats). In normotensive animals the metal-nonoate maintained blood pressure at basal level both following acute administration and after 30 days of treatment. In SHR, Ni(PipNONO)Cl reduced blood pressure in the dose range of 3-10mg/kg. When compared with a commercial NONOate, DETA/NO, used at the same doses, Ni(PipNONO)Cl was more active in reducing blood pressure in SHR than DETA/NO in the first two weeks, while the effect of the two molecules was similar in the third and fourth week. The degradation and control compound Ni(Pip)Cl2 had no effect on blood pressure and heart rate in same animal models. Remarkably, the blood pressure reduction induced by the new NO-donor Ni(PipNONO)Cl does not evoke changes in the heart rate and tolerance. Considering the mechanisms of vascular protection, 30 days of administration of Ni(PipNONO)Cl improved endothelial function in SHR by upregulating endothelial NO synthase (eNOS) through increased eNOS protein levels and downregulated Caveolin-1 (Cav-1), and by increasing superoxide dismutase 1 (SOD1) protein level in aortae. In cultured endothelial cells Ni(PipNONO)Cl restored the cell functions (cytoskeletal protein expression, migration and proliferation) altered by the inflammatory mediator interleukin-1β (IL-1β), impairing the endothelial to mesenchimal transition. In conclusion, Ni(PipNONO)Cl maintained unaltered blood pressure in normotensive mice and rats, and it exerted anti-hypertensive effect in SHR through the restoration of vascular endothelial protective functions. PMID:27063892

  4. Proteomics Analysis of Molecular Risk Factors in the Ocular Hypertensive Human Retina

    PubMed Central

    Yang, Xiangjun; Hondur, Gözde; Li, Ming; Cai, Jian; Klein, Jon B.; Kuehn, Markus H.; Tezel, Gülgün

    2015-01-01

    Purpose To better understand ocular hypertension–induced early molecular alterations that may determine the initiation of neurodegeneration in human glaucoma, this study analyzed retinal proteomic alterations in the ocular hypertensive human retina. Methods Retina samples were obtained from six human donors with ocular hypertension (without glaucomatous injury) and six age- and sex-matched normotensive controls. Retinal proteins were analyzed by two-dimensional LC-MS/MS (liquid chromatography and linear ion trap mass spectrometry) using oxygen isotope labeling for relative quantification of protein expression. Proteomics data were validated by Western blot and immunohistochemical analyses of selected proteins. Results Out of over 2000 retinal proteins quantified, hundreds exhibited over 2-fold increased or decreased expression in ocular hypertensive samples relative to normotensive controls. Bioinformatics linked the proteomics datasets to various pathways important for maintenance of cellular homeostasis in the ocular hypertensive retina. Upregulated proteins included various heat shock proteins, ubiquitin proteasome pathway components, antioxidants, and DNA repair enzymes, while many proteins involved in mitochondrial oxidative phosphorylation exhibited downregulation in the ocular hypertensive retina. Despite the altered protein expression reflecting intrinsic adaptive/protective responses against mitochondrial energy failure, oxidative stress, and unfolded proteins, no alterations suggestive of an ongoing cell death process or neuroinflammation were detectable. Conclusions This study provides information about ocular hypertension–related molecular risk factors for glaucoma development. Molecular alterations detected in the ocular hypertensive human retina as opposed to previously detected alterations in human donor retinas with clinically manifest glaucoma suggest that proteome alterations determine the individual threshold to tolerate the ocular

  5. Shared medical appointments in pulmonary hypertension.

    PubMed

    Rahaghi, Franck F; Chastain, Veronica L; Benavides, Rosanna; Ferrer, Gustavo; Ramirez, Jose; Mehta, Jinesh; Oliveira, Eduardo; Smolley, Laurence

    2014-03-01

    We aimed to adapt the shared medical appointment (SMA) model to the care of pulmonary hypertension (PH) patients and evaluate patient satisfaction. Our SMA team included a PH specialist, a PH nurse, and one research fellow. Eight to twelve PH patients with a family member were invited during office visits and by phone calls. Attendance was verified and encouraged by phone calls and informational letters. The meetings started with a 30-minute presentation on various PH topics, which was followed by each patient's individual visit and a focused examination in front of the group, allowing group questions and interaction. Of the total number of patients (n = 53), 84% stated that they would attend a future SMA. The care provided was rated excellent to very good by 98% of the patients. Ninety-two percent stated that they improved their understanding of the disease and treatment options, and 59% acknowledged a preference for the group visit over the private visit. Twenty-five percent of patients stated that they were very likely to likely to some extent to agree to change or seek a change in treatment modality on the basis of conversation with other patients in the SMA. The majority of our patients expressed no privacy concerns before the meeting (76%), and even more expressed no such concerns afterward (88%). In conclusion, the SMA model allows PH patients to increase understanding of their disease process while integrating peer support, promoting social interaction, and addressing patients' emotional needs. Other (rare) pulmonary diseases may benefit from this model. PMID:25006421

  6. GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

    PubMed Central

    Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

    2015-01-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  7. Perspective on hypertension in the elderly.

    PubMed Central

    Whitcomb, B.; Byyny, R. L.

    1990-01-01

    More than half of elderly men and women have hypertension, leading to a significant risk of increased morbidity and mortality. The cause of hypertension in this age group is unknown. Left ventricular hypertrophy is frequently present, often associated with diastolic dysfunction. Systolic hypertension in the elderly increases the risk of cardiovascular disease, but there are no good data to show that the treatment of isolated systolic hypertension reduces the morbidity or mortality. Good evidence indicates that antihypertensive treatment in this group decreases cardiovascular morbidity and mortality up to age 80, so most elderly hypertensive patients should be treated. An empiric trial of nonpharmacologic therapy can be initiated in those with mild hypertension and no cardiovascular disease, but most patients will require drug therapy. Most elderly hypertensive patients have accompanying illnesses for which they may or may not be taking medications. Some antihypertensive drugs exacerbate coexisting diseases while others augment treatment regimens. Similarly, drugs may interact in a beneficial or adverse way. Finally, drug metabolism is altered by age, leading to problems with toxicity or diminished efficacy. The choice of medication should be based on all such considerations, including the cost and convenience of the drugs available. PMID:2190414

  8. Non-interventional management of resistant hypertension

    PubMed Central

    Doumas, Michael; Tsioufis, Costas; Faselis, Charles; Lazaridis, Antonios; Grassos, Haris; Papademetriou, Vasilios

    2014-01-01

    Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the “uncontrollable” part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients. PMID:25349652

  9. Gut dysbiosis is linked to hypertension.

    PubMed

    Yang, Tao; Santisteban, Monica M; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J; Raizada, Mohan K; Mohamadzadeh, Mansour

    2015-06-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  10. [Rare forms of hypertension : From pheochromocytoma to vasculitis].

    PubMed

    Haller, H; Limbourg, F; Schmidt, B M; Menne, J

    2015-03-01

    Secondary hypertension affects only 5-10 % of hypertensive patients. Screening is expensive and time-consuming and should be performed only in patients for whom there is a high clinical suspicion of secondary hypertension. Clinical signs of secondary forms of hypertension are new-onset hypertension in patients without other risk factors (i.e., family history, obesity, etc.), sudden increase of blood pressure (BP) in a previously stable patient, increased BP in prepubertal children, resistant hypertension, and severe hypertension or hypertensive emergencies. In adults, renal parenchymal and vascular diseases as well as obstructive sleep apnea are the most common causes of secondary hypertension. Medication-induced hypertension and non-adherence to medication have to be ruled out. Of the endocrine causes associated with hypertension, primary aldosteronism is the most common. Other endocrine causes of hypertension such as thyroid disease (hypo- or hyperthyroidism), hypercortisolism (Cushing's syndrome), hyperparathyroidism, and pheochromocytoma are rare. Monogenetic forms of hypertension are mostly of tubular origin and associated with alterations in mineralocorticoid handling or signaling. Rare causes of hypertension also include inflammatory vascular disease. Acute forms of vasculitis may present as "malignant" hypertension with associated thrombotic microangiopathy and organ damage/failure. It is important to diagnose these rare forms of hypertension in order to prevent acute organ damage in these patients or unnecessary invasive treatment strategies. PMID:25700646

  11. An approach to the young hypertensive patient.

    PubMed

    Mangena, P; Saban, S; Hlabyago, K E; Rayner, B

    2016-01-01

    Hypertension is the leading cause of death worldwide. Globally and locally there has been an increase in hypertension in children, adolescents and young adults<40 years of age. In South Africa, the first decade of the millennium saw a doubling of the prevalence rate among adolescents and young adults aged 15-24 years. This increase suggests that an explosion of cerebrovascular disease, cardiovascular disease and chronic kidney disease can be expected in the forthcoming decades. A large part of the increased prevalence can be attributed to lifestyle factors such as diet and physical inactivity, which lead to overweight and obesity. The majority (>90%) of young patients will have essential or primary hypertension, while only a minority (<10%) will have secondary hypertension. We do not recommend an extensive workup for all newly diagnosed young hypertensives, as has been the practice in the past. We propose a rational approach that comprises a history to identify risk factors, an examination that establishes the presence of target-organ damage and identifies clues suggesting secondary hypertension, and a limited set of basic investigations. More specialised tests should be performed only where there is a clinical suspicion that a secondary cause for hypertension exists. T