Abstract:
BACKGROUND:We previously showed that young transgenic mice overexpressing preproendothelin-1 specifically in endothelial cells had hypertrophic remodeling, endothelial dysfunction, increased vascular NADPH oxidase activity, and inflammation in mesenteric small arteries without blood pressure (BP) elevation compared to nontransgenic wild-type littermates. To assess the consequences of salt-loading and the role of endothelin receptors, we investigated the effects of these on vascular structure, function, and oxidative stress in mesenteric arteries in salt-loaded transgenic mice treated with endothelin receptor antagonists. METHODS:Ten-month-old male transgenic and wild-type littermates were salt-loaded (4% NaCl) and treated with endothelin subtype A receptor antagonist (ET(A)RA, ABT-627, 5 mg/kg per day), endothelin subtype B receptor antagonist (ET(B)RA; A-192621, 30 mg/kg per day), or ET(A)/BRA (bosentan, 100 mg/kg per day) for 4 weeks. BP was measured by radiotelemetry, vascular reactivity of mesenteric small arteries was studied on a pressurized myograph, and vascular NADPH oxidase activity was studied by lucigenin chemiluminescence. RESULTS:Transgenic+salt mice had significantly increased BP compared with wild-type+salt mice, which was prevented by ET(A)RA and dual ET(A/B)RA but further increased by ETB antagonism. Increased small artery media/lumen ratio of transgenic+salt mice was significantly decreased only by dual ET(A/B)RA (P < 0.01), whereas no differences were found in media cross-sectional area. Impaired maximal relaxation of small arteries to acetylcholine was significantly prevented with ET(A)RA and ET(A/B)RA (P < 0.05). N(omega)-nitro-L-arginine methyl ester-induced reduction of acetylcholine maximal relaxation was partially prevented by ET(A)RA, completely prevented by dual, and partially restored by vitamin C preincubation following dual ET(A/B)RA. The blunted endothelin-1 contractile response of small arteries found in transgenic+salt mice was partially restored by ET(A)RA and completely prevented by dual ET(A/B)R antagonism. The vasoconstrictor response to endothelin-1 was not altered in the presence or absence of ET(B)RA. Increased vascular NADPH oxidase activity of transgenic+salt mice was further increased by ET(B)RA but returned to levels seen in wild-type+salt mice under either ET(A)RA and ET(A/B)RA. CONCLUSION:Transgenic+salt mice with endothelin-1 overexpression have structural alterations of mesenteric resistance vessels, endothelial dysfunction due to reduced nitric oxide bioavailability, a reduced responsiveness to endothelin-1, and enhanced vascular NADPH oxidase activity. ET(B)RA further exacerbated these effects, whereas ET(A)RA significantly improved but did not normalize them in chronically salt-loaded transgenic mice with endothelial cell human endothelin-1 overexpression. Salt and endothelin-1 overexpression have deleterious additive effects on vascular remodeling mediated by ET(A)R and ET(B)R. ET(B)R probably located in the endothelium, however, also exerts beneficial effects on endothelial function in this experimental paradigm. The present study provides the first in-vivo demonstration that endothelin-1 overexpression when associated with high-salt intake results in enhanced endothelial dysfunction and vascular remodeling of resistance vessels, and contributes to elevated BP, via ET(A)R and ET(B)R.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Amiri F,Ko EA,Javeshghani D,Reudelhuber TL,Schiffrin ELdoi
10.1097/HJH.0b013e328338bb8bsubject
Has Abstractpub_date
2010-06-01 00:00:00pages
1243-51issue
6eissn
0263-6352issn
1473-5598journal_volume
28pub_type
杂志文章abstract::: The hypertension paradigm has contributed to a dramatic reduction in CVD mortality. This has been achieved by applying average results of population studies to identify a target population and design a common intervention to achieve a BP goal. Progressive lowering of the BP threshold has expanded the fraction of per...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002375
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVE:To investigate the effects of prolonged hypertension in the absence of cardiac hypertrophy on the blood pressure-heart rate reflex during acute and chronic NO synthase blockade. METHODS:Male Wistar rats were treated acutely with N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg intraperitoneally) or ch...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199610000-00009
更新日期:1996-10-01 00:00:00
abstract::An Na+,K+-ATPase inhibitor possessing inhibitory activity against the specific binding of ouabain to Na+,K+-ATPase has been purified from the plasma of acutely saline-infused hogs. The purification was performed by a combination of Amberlite XAD-2 adsorption chromatography and five steps of high-pressure liquid chroma...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198704000-00014
更新日期:1987-04-01 00:00:00
abstract:OBJECTIVE:We attempted to determine a valid pharmacological approach for the control of high blood pressure in obese hypertensive patients using two antihypertensive agents with different pharmacological actions. DESIGN:Thirty-two obese hypertensive black women were randomly treated with chlorthalidone or clonidine to...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-199205000-00013
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS) are the most common causes of renovascular hypertension. So far, FMD is believed to cause hypertension via similar mechanisms as in ARAS, that is, a decrease in renal blood flow, which subsequently leads to increased renin secreti...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001243
更新日期:2017-04-01 00:00:00
abstract:OBJECTIVE:To investigate the relationship between admission SBP and subsequent cardiovascular and all-cause mortality in older patients hospitalized for acute coronary syndrome (ACS). METHODS:This is a retrospective observational study. Data from the CBD Bank (Cardiovascular Center Beijing Friendship Hospital Database...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002737
更新日期:2020-11-16 00:00:00
abstract:OBJECTIVES:Recent studies in homogenized hearts suggest that chymase rather than angiotensin converting enzyme (ACE) is responsible for cardiac angiotensin I to angiotensin II conversion. We investigated in intact rat hearts whether (i) enzymes other than ACE contribute to angiotensin I to angiotensin II conversion and...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200105000-00017
更新日期:2001-05-01 00:00:00
abstract:OBJECTIVE:Abnormal vascular reactivity contributes to the pathophysiology of hypertension and hypertension-related organ damage. As the dietary content of fatty acids may affect the vascular responses, we investigated the relationship of endothelium-independent and endothelium-dependent vasodilation with the fatty acid...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000495
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:To evaluate the mean levels of blood pressure and hypertension (> or = 140 mmHg systolic or > or = 90 mmHg diastolic pressure or on treatment for hypertension) in the adult English population, and to evaluate any changes in the efficacy of hypertension management between 1994 and 2003. DESIGN/METHODS:Cross-s...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000226210.95936.bc
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:Hypertension-induced renal injury is characterized by inflammation, fibrosis and proteinuria. Previous studies have demonstrated that N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) inhibits renal damage following diabetes mellitus and antiglomerular basement membrane nephritis. However, its effects on low-renin hyperten...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834103ee
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:C-reactive protein (CRP) both reflects and participates in inflammation, and its circulating concentration marks cardiovascular risk. Here we sought to understand the role of heredity in determining CRP secretion. METHODS:CRP, as well as multiple facets of the metabolic syndrome, were measured in a series o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328011753e
更新日期:2007-02-01 00:00:00
abstract:OBJECTIVES:Increased endothelial production of reactive oxygen species and decreased nitric oxide bioactivity, associated with the upregulation of monocyte chemoattractant protein (MCP)-1 and lectin-like oxidized low-density lipoprotein receptor (LOX)-1, link hypertension with atherogenesis. We investigated whether the...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f3e39d
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:The usefulness of the hypertensive retinopathy classification by Keith-Wagener-Barker (KWB) in clinical practice remains controversial. The simplified Mitchell-Wong grading, combining the two initial KWB' grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding t...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000702
更新日期:2015-11-01 00:00:00
abstract:OBJECTIVE:Although several studies have reported an association between microalbuminuria and pulse wave velocity in patients with hypertension or diabetes, there have been no reports of their significance in apparently healthy individuals. METHODS:Microalbuminuria and brachial-ankle PWV (baPWV) were investigated in a ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834b5627
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVE:The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. METHODS:The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we an...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32834f6b11
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). METHODS:We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure w...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200018040-00008
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVES:Aortic (central) blood pressure (BP) differs from brachial BP and may be a superior predictor of cardiovascular events. However, its measurement is currently restricted to research settings, owing to a moderate level of operator dependency. We tested a new noninvasive device in a large UK cohort. The device ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000082
更新日期:2014-04-01 00:00:00
abstract::This paper describes the kinetics of the Na(+)-K+ pump and the Na(+)-K(+)-Cl- cotransport in sodium-loaded erythrocytes and of the Na(+)-K(+)-Cl- cotransport in erythrocyte inside-out vesicles (IOV) from Milan hypertensive (MHS) and normotensive (MNS) rats in order to evaluate the possible role of intracellular factor...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199108000-00003
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. OBJECTIVE:To examine the relationship between coffee in...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/01.hjh.0000249696.19360.be
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:The inverse association between socioeconomic status (SES) and cardiovascular disease (CVD) risk is well documented. Aortic stiffness assessed by aortic pulse wave velocity (PWV) is a strong predictor of CVD events. However, no previous study has examined the effect of SES on arterial stiffening over time. Th...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001057
更新日期:2016-10-01 00:00:00
abstract:OBJECTIVE:To clarify the spectrum of the left ventricular responses in hypertension in man by means of coupled analysis of elastances. In the present study we analysed the 'functional' coupling of the left ventricle and the arterial system in terms of the arterial effective elastance (E(a)) divided by a value of end-sy...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVES:It is estimated that there are more than 16 million adults with drug-resistant hypertension in China. Nevertheless, the prevalence of and risk factors for primary aldosteronism, a highly curable condition among adults with drug-resistant hypertension, has not been fully investigated. METHODS:Between January...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328360ddf6
更新日期:2013-07-01 00:00:00
abstract:DESIGN:Because of uncertainties regarding the complete antihypertensive mechanism of action of beta-adrenoceptor antagonists, the present study determined whether vagal afferent neurons of humans and rats possess beta-adrenoceptors. Such a location would provide an appropriate target for beta-blockers to modulate neuro...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199506000-00009
更新日期:1995-06-01 00:00:00
abstract:BACKGROUND:Despite data from animal models and observational studies that are generally supportive for the soy/isoflavones lowering blood pressure (BP) and improving vascular function, the current findings from clinical trials are still inconclusive. OBJECTIVES:To examine whether soy protein with isoflavones or isofla...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e32835c0905
更新日期:2013-02-01 00:00:00
abstract::The effects of essential fatty acid deficiency (EFAD) on vascular reactivity to vasoconstrictor stimuli were studied in rat autoperfused hindquarters. Weanling male Sprague-Dawley rats (aged 21 days) were fed diets containing 8% (weight/weight) of stearax plus 2% safflower oil (control diet) or 10% stearax (EFAD diet)...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract:BACKGROUND:The urinary isoflavonoid equol inhibits membrane Na-K-Cl cotransporters at similar concentrations to those at which furosemide inhibits them, but the significance of this action is not known. OBJECTIVE:To investigate the potential salidiuretic and vascular actions of equol in the rat. METHODS:Renal functio...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199715110-00015
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVES:The role of the baroreflex function in the pathogenesis of hemodialysis-associated hypotension is controversial. Complex demodulation technique (CDM), providing continuous assessment of the amplitude of cardiovascular oscillation over time, is particularly suitable to assess dynamic changes in autonomic nerv...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328332b7af
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVES:To explore the association of different types of blood pressure (BP) variability measures estimated from either short-term ambulatory reading-to-reading or long-term clinic visit-to-visit BP records with long-term survival in an elderly treated hypertensive population. METHODS:A subset of patients (n = 508)...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001652
更新日期:2018-05-01 00:00:00
abstract::The relationships between five erythrocyte cation transport systems (Na(+)-K+ pump, Na(+)-K+ cotransport, Na(+)-Li+ countertransport and Na+ and K+ passive permeabilities) and plasma lipids (total plasma cholesterol, high-density lipoprotein cholesterol and triglycerides) were investigated in 129 male adult subjects w...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199010000-00002
更新日期:1990-10-01 00:00:00
abstract:UNLABELLED:PURPOSE IDENTIFICATION: Inter-individual variability in blood pressure response to treatment is well documented, but a clinically useful means to distinguish responders from non-responders has been elusive. With the advent of new technologies and genomic knowledge, more investigators are seeking to identify ...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/01.hjh.0000173510.52987.68
更新日期:2005-07-01 00:00:00