Hypertension
0194-911X
1524-4563
Mỹ
Cơ quản chủ quản: LIPPINCOTT WILLIAMS & WILKINS , Lippincott Williams and Wilkins Ltd.
Lĩnh vực:
Internal Medicine
Phân tích ảnh hưởng
Thông tin về tạp chí
Hypertension delivers some of the best high blood pressure-related articles in each monthly issue. Articles are focused on basic science, clinical treatment, and prevention of hypertension and related cardiovascular, metabolic and renal diseases, and are the papers which will prove their significance for years to come. Online subscriptions are available to members of the American Heart Association/American Stroke Association as a benefit of membership depending on membership level.
Các bài báo tiêu biểu
Peroxisome Proliferator-Activated Receptor-α and Receptor-γ Activators Prevent Cardiac Fibrosis in Mineralocorticoid-Dependent Hypertension Peroxisome proliferator-activated receptor (PPAR) activation may prevent cardiac hypertrophy and inhibit production of endothelin-1 (ET-1), a hypertrophic agent. The aim of this in vivo study was to investigate the effects of PPAR activators on cardiac remodeling in DOCA-salt rats, a model overexpressing ET-1. Unilaterally nephrectomized 16-week-old Sprague-Dawley rats (Uni-Nx) were randomly divided into 4 groups: control rats, DOCA-salt, DOCA-salt+rosiglitazone (PPAR-γ activator, 5 mg/kg per day), and DOCA-salt+fenofibrate (PPAR-α activator, 100 mg/kg per day). After 3 weeks of treatment, mean arterial blood pressure was significantly increased in DOCA-salt by 36 mm Hg. Mean arterial blood pressure was normalized by coadministration of rosiglitazone but not by fenofibrate. Both PPAR activators prevented cardiac fibrosis and abrogated the increase in prepro–ET-1 mRNA content in the left ventricle of DOCA-salt rats. Coadministration of rosiglitazone or fenofibrate failed to prevent thickening of left ventricle (LV) walls as measured by echocardiography and the increase in atrial natriuretic peptide mRNA levels. However, rosiglitazone and fenofibrate prevented the decrease in LV internal diameter and thus concentric remodeling of the LV found in DOCA-salt rats. Taken together, these data indicate a modulatory role of PPAR activators on cardiac remodeling in mineralocorticoid-induced hypertension, in part associated with decreased ET-1 production.
Tập 42 Số 4 - Trang 737-743 - 2003
Angiotensin II Regulation of Collagen Type I Expression in Cardiac Fibroblasts
Angiotensin II (Ang II)–mediated stimulation of fibroblast growth and collagen type I synthesis is believed to be an important component of the cardiac remodeling process in hypertension and chronic ischemia. Ang II–mediated oxidative stress could be important in enhanced fibroblast growth and collagen formation. Accordingly, we postulated that the PPAR-γ ligand, pioglitazone, which is known to modulate oxidative stress, would alter Ang II–induced formation of collagen type I in cardiac fibroblasts. Cardiac fibroblasts were treated with different concentrations (10
−8
to 10
−6
M) of Ang II for different times (6 hours, 12 hours, and 24 hours). Ang II increased the expression of collagen type I in a concentration- and time-dependent fashion (
P
<0.01 versus control). Ang II also decreased the expression and activity of matrix metalloproteinase (MMP)-1 (MMP-1,
P
<0.05 versus control). These effects of Ang II were attenuated by pretreatment of cells with pioglitazone (10 μmol/L). Ang II stimulated the intracellular generation of reactive oxygen species (ROS), and this effect was also attenuated by pioglitazone. Ang II treatment activated the redox-sensitive transcription factor NF-κB, and pioglitazone pretreatment blocked this effect of Ang II. Ang II also activated another transcription factor, AP-1, but this effect of Ang II was not modulated by pioglitazone. In other experiments, we observed that trolox, the water soluble analog of vitamin E, attenuated the effects of Ang II on the expression of collagen type I and MMP-1, in a manner similar to pioglitazone. Thus, pioglitazone attenuates Ang II-mediated collagen type I synthesis in cardiac fibroblasts. The effects of pioglitazone are mediated by the modulation of ROS release and redox-sensitive transcription factor NF-κB.
Tập 44 Số 5 - Trang 655-661 - 2004
Flow-Mediated Vasodilation and Plasma Fibronectin Levels in Preeclampsia
Abstract
—To clarify the vascular endothelial function in pregnant women with hypertensive disorders, we assessed the flow-mediated vasodilation in the radial artery and compared it with plasma fibronectin levels. We determined flow-mediated vasodilation by measuring the change in radial artery diameter during hyperemia in 58 normal pregnant women, 22 preeclamptic pregnant women, and 15 pregnant women with chronic hypertension. In 41 of the 95 pregnant women, we measured the plasma fibronectin levels. Flow-mediated vasodilation in preeclamptic women was significantly less than that in normal pregnant women (
P
<0.001). In chronic hypertensive women, flow-mediated vasodilation was significantly less than that in normal pregnant women (
P
<0.001) but more than that in preeclamptic women (
P
<0.001). Flow-mediated vasodilation showed significant negative correlation with plasma fibronectin levels (
P
<0.001,
r
=0.73). Our results indicate that the endothelial function can be noninvasively assessed in pregnant women with hypertensive disorders by measuring the flow-mediated vasodilation of the radial artery with high-resolution ultrasound.
Tập 36 Số 3 - Trang 400-404 - 2000
Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase
Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37–1.73]; combined
P
=2.58 · 10
−13
). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25–1.44;
P
=1.032 · 10
−14
). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16–3.66) for systolic and 1.40 (95% CI: 0.25–2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to
rs3918226,
suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
Tập 59 Số 2 - Trang 248-255 - 2012
Augmentation of cardiopulmonary baroreflex control of forearm vascular resistance in borderline hypertension. Arterial baroreflex control of heart rate is impaired in young men with borderline or mild hypertension. Despite this impairment, these subjects often have exaggerated increases in vascular resistance during orthostatic stress. We considered the possibility that this exaggerated reflex vasoconstriction might reflect augmented cardiopulmonary baroreflex control of vascular resistance in borderline hypertension (BHT). Accordingly, we studied cardiopulmonary baroreflex control of forearm vascular resistance in nine BHT men with blood pressure intermittently above 150/90 mm Hg and in seven normotensive (NT) men. Cardiopulmonary baroreceptor input was reduced with lower body negative pressure (LBNP-5 to-20 mm HG), which decreases cardiac filling pressures. Baseline mean arterial pressure was 99 /+- 3 mm Hg (mean /+- SE) in BHT vs 83 /+- 2 mm Hg in NT (p less than 0.05). Baseline forearm resistance was also higher in BHT than in NT: 19 /+- 2 vs 13 /+-1 mm Hg/ml/min/100 ml or units (p less than 0.05). Reflex increases in forearm resistance during LBNP were greater (p less than 0.05) in BHT than in NT 8.6 /+- 1.7 vs 4.5 /+- 1.1 units during LBNP-20). Increases in arterial pressure and forearm resistance during a cold pressor test were not significantly different in the two groups. Thus, the augmented response to LBNP could not be attributed to a nonspecific influence of increased baseline resistance or a generalized abnormality in reflex control. In summary, the results of this study suggest that there is augmentation of the tonic inhibitory influence of cardiopulmonary baroreceptors in humans with BHT.
Tập 4 Số 1 - Trang 39-46 - 1982
Hypertension Produced by Reductions in Uterine Perfusion in the Pregnant Rat Inflammatory cytokines such as tumor necrosis factor (TNF)-α are elevated in preeclamptic women and are thought to be an important link between placental ischemia and endothelial dysfunction. The purpose of this study was to determine the role of TNF in mediating hypertension in response to chronic reductions in uterine perfusion (RUPPs) in pregnant rats. Arterial pressure was significantly higher in RUPP rats (138±1 mm Hg) than in pregnant rats (107±1 mm Hg). Serum TNF-α levels in the RUPP rats were 17±4 pg/mL compared with 8±1 pg/mL in normal pregnant rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma TNF-α on renal and systemic hemodynamics in pregnant rats, we infused TNF-α for 5 days at a rate of 50 ng/d during days 14 to 19 of gestation in pregnant rats. Serum levels were 7±2 pg/mL in the control pregnant rats and 14±2 pg/mL in the TNF-α–treated pregnant rats. Mean arterial pressure was higher in the TNF-α–treated pregnant rats (123±3 mm Hg) compared with pregnant controls (96±3 mm Hg) at day 19 of gestation. TNF-α increased renal vascular resistance in pregnant rats by 182%. Renal plasma flow was 5.4±1.2 mL/min in the TNF-α–treated group and 9.2±1.6 mL/min in the control group. Glomerular filtration rate was 1.7±0.4 mL/min in the TNF-α–treated group and 2.6±0.4 mL/min in the control group. In summary, these data suggest that TNF-α may play an important role in mediating the increased arterial pressure in response to chronic RUPPs in pregnant rats.
Tập 46 Số 4 - Trang 1022-1025 - 2005
Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Three isozymes of nitric oxide (NO) synthase (EC 1.14.13.39) have been identified and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells) are encoded for by three different genes located on chromosomes 12, 17, and 7, respectively. The deduced amino acid sequences of the human isozymes show less than 59% identity. Across species, amino acid sequences for each isoform are well conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use L-arginine and molecular oxygen as substrates and require the cofactors NADPH, 6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin mononucleotide. They all bind calmodulin and contain heme. Isoform I is constitutively present in central and peripheral neuronal cells and certain epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves. It has also been implicated in neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase can be induced with lipopolysaccharide and cytokines in a multitude of different cells. Based on sequencing data there is no evidence for more than one inducible isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large amounts of NO that has cytostatic effects on parasitic target cells by inhibiting iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is involved in the pathophysiology of autoimmune diseases and septic shock. Isoform III of NO synthase has been found mostly in endothelial cells. It is constitutively expressed, but expression can be enhanced, eg, by shear stress. Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps blood vessels dilated, prevents the adhesion of platelets and white cells, and probably inhibits vascular smooth muscle proliferation.
Tập 23 Số 6_pt_2 - Trang 1121-1131 - 1994
Endothelial mechanism in the vascular action of hydralazine. Relaxation of precontracted isolated chains of aortic rings with intact endothelium and in those with the endothelium removed was studied in response to various antihypertensive vasodilator drugs. Of the drugs tested--nitroprusside, nitroglycerin, prazosin, minoxidil, diazoxide and hydralazine--only the vascular relaxant effects of hydralazine were found to be dependent, in part, on the presence of intact endothelium. The endothelial component of the hydralazine response represented a major contribution to the net relaxant effect on the vascular smooth muscle, particularly at lower concentrations, 90 nM to 1 microM, which are also clinically relevant.
Tập 5 Số 2_pt_2 - 1983
Plasma concentration and acetylator phenotype determine response to oral hydralazine. The vasodepressor response to single and multiple oral doses of hydralazine, 1 mg/kg, was studied in hypertensive patients. The concentration of hydralazine in plasma was measured both by a newly developed specific and a nonspecific assay similar to those used in previous studies. Acetylator phenotype was determined following oral sulfamethazine. Plasma hydralazine concentration peaked at 1 hour after administration and was undetectable 2 hours later. Apparent hydralazine was present in plasma in higher concentration and for a longer duration than hydralazine. The peak decreases in blood pressure (BP) were proportional to plasma hydralazine concentration following administration of both single and multiple doses and were substantially maintained for 8 hours. In contrast there was no significant correlation between decreases in BP and apparent hydralazine concentrations. The plasma concentration of hydralazine after a standard oral dose varied by as much as 15-fold among individuals and was lower in rapid than slow acetylator phenotype patients. The BP responses were positively correlated with plasma hydralazine concentrations and inversely correlated with acetylator indices. Low plasma concentrations may account for poor responses of some patients to conventional oral doses of hydralazine. The applicability of acetylator phenotyping for individualization of hydralazine dosage regimens merits further evaluation.
Tập 3 Số 5 - Trang 580-585 - 1981