Abstract:
OBJECTIVE:The major advantage of dual inhibitors of neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) is their ability to lower blood pressure irrespective of renin or volume status. The aim of this study was to determine whether dual NEP/ACE inhibition produces different effects on cardiovascular structure and fibrosis, hormonal parameters and inhibition of tissue enzymes compared with selective inhibition of ACE and NEP in the spontaneously hypertensive rat (SHR). METHODS:Male SHRs received the dual NEP/ACE inhibitor (S21402, 100 mg/kg per day), the ACE inhibitor (captopril, 50 mg/kg per day), the NEP inhibitor (SCH42495, 60 mg/kg per day) or vehicle for 2 weeks. RESULTS:S21402 produced equivalent blood pressure lowering effects to captopril (vehicle, 220 +/- 1 mmHg; S21402, 189 +/- 2 mmHg; captopril, 187 +/- 3 mmHg), but was a more effective antihypertensive agent than SCH42495 (214 +/- 2 mmHg, P< 0.01). All treatments reduced left ventricular mass (P< 0.05) and cardiac fibrosis (P< 0.01). S21402 inhibited renal NEP and ACE (P< 0.01), SCH42495 inhibited renal NEP (P < 0.01), and captopril inhibited renal ACE (P< 0.01). Captopril and S21402 increased plasma renin activity (P< 0.05), but the rise with S21402 was attenuated compared with that caused by captopril (P< 0.01). All treatments reduced plasma aldosterone levels (P< 0.01), and NEP inhibition with SCH42495 and S21402 increased plasma atrial natriuretic peptide (ANP; P< 0.05). CONCLUSIONS:These results indicate that selective NEP inhibition has major benefits in the regression of cardiac hypertrophy and reduction of fibrosis but has limited antihypertensive effects. The dual NEP/ACE inhibitor S21402 offered no advantage over the selective ACE inhibitor in terms of blood pressure reduction, or attenuation of cardiac hypertrophy and fibrosis, but did increase plasma ANP and blunted the reactive rise in renin with ACE inhibition. Further studies are needed to determine whether more complete blockade of the renin-angiotensin system with dual NEP/ACE inhibition results in additional benefits in terms of morbidity and mortality in cardiovascular disease.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Farina NK,Johnston CI,Burrell LMdoi
10.1097/00004872-200018060-00013subject
Has Abstractpub_date
2000-06-01 00:00:00pages
749-55issue
6eissn
0263-6352issn
1473-5598journal_volume
18pub_type
杂志文章abstract:BACKGROUND:A cardiac angiotensin II-generating system has been suspected to be involved in various cardiac pathological conditions. Both angiotensin converting enzyme and human chymase can convert angiotensin I to angiotensin II. OBJECTIVE:To clarify the relative contributions of these two enzymatic pathways to angiot...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199715090-00003
更新日期:1997-09-01 00:00:00
abstract:OBJECTIVE:The main objective was to examine the role of hemodynamics in rat aortic and left ventricular hypertrophy produced by sinoaortic denervation (SAD). DESIGN AND METHODS:Rats were examined at different times after SAD or sham operation (Sham). Hemodynamics were recorded continuously in conscious unrestrained ra...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200209000-00033
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND AND METHOD:This study evaluated the effects of a linear block strength training programme on the parameters of cardiac remodelling in spontaneously hypertensive rats. Thirty-nine rats were equally distributed in four groups: normotensive sedentary, normotensive trained, hypertensive sedentary and hypertensiv...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002188
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:To investigate the effects of the interaction between adenosine receptors and renal nerves on urinary sodium excretion and glomerular filtration rate. METHODS AND DESIGN:The effects on water and sodium excretion and glomerular filtration rate of A1 [2-chloro-N6-cyclopentyl-adenosine (CCPA)] and A2 [2-hesiny...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199715120-00090
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:Work stress contributes to risk of coronary heart disease and hypertension. This study tested the influence of job control on ambulatory blood pressure, and ratings of perceived stress and happiness in men and women systematically sampled by socio-economic status from the Whitehall II epidemiological cohort. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200405000-00012
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to identify, describe, and evaluate the available cardiovascular disease risk prediction models developed or validated in the hypertensive population. METHODS:MEDLINE and the Web of Science were searched from database inception to March 2019, and all reference lists of included arti...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002442
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:It is not well known which exercise intensity is needed to obtain blood pressure reductions in response to endurance training. We therefore compared the effect of training at lower and higher intensity on blood pressure, and, in addition on other cardiovascular risk factors, in at least 55-year-old sedentary ...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e328322cf60
更新日期:2009-04-01 00:00:00
abstract::Arterial aging is associated with a progressive increase in aortic stiffening, which results in a rise in central aortic pressures. Traditionally, blood pressure (BP)-lowering therapy has been directed at brachial rather than central pressures. However, a key contemporary question is whether this strategy is optimal i...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/HJH.0b013e328353e523
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVE:This study was designed to evaluate the capacity of norepinephrine (NE) to induce hypertrophic remodeling of small arteries in rats, and to determine the involvement of endothelin (ET) to initiate and maintain it. DESIGN AND RESULTS:Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced a simil...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200110000-00014
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVE:It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mecha...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e3280287a72
更新日期:2007-04-01 00:00:00
abstract::Medical records were examined for 1935 patients who presented sequentially to a hypertension clinic between 1971 and 1981. Patients were classified according to whether they were on a beta-blocker, methyldopa, a potassium-losing diuretic, or whether they had discontinued any of these treatments. Age-standardized morta...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198907000-00009
更新日期:1989-07-01 00:00:00
abstract:BACKGROUND:Ambulatory blood pressure (BP) monitoring (ABPM) detects subjects with normal clinic but high ambulatory 24-h BP, that is, masked hypertension. METHODS:One hundred and thirty newly diagnosed obstructive sleep apnea syndrome (OSAS) patients, free of recognized cardiovascular disease were included (111 men, a...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f55049
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVES:To test whether the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene is of functional relevance in humans by altering endothelium-dependent vasodilation. BACKGROUND:The Asp298 variant of the eNOS gene product has been associated with arterial hypertension, coronary artery disease ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200018120-00010
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVES:The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. M...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328347e333
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:To determine whether obese hypertensive patients manifest a diminished regional vasodilator response to an oral glucose challenge. METHODS:Nineteen obese hypertensives (body mass index 34.1 +/- 1.3 kg/m2, blood pressure 144 +/- 3/96 +/- 2 mmHg) and 13 lean controls (23.6 +/- 0.3 kg/m2, 127 +/- 4/83 +/- 3 mmH...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract:OBJECTIVE:To conduct a longitudinal evaluation of the central haemodynamic adaptations of normal pregnancy. METHODS:This was a prospective longitudinal study involving healthy, normotensive women who were having an uncomplicated, singleton pregnancy. Brachial and central SBP, DBP, mean arterial pressure (MAP), brachia...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001768
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of angiotensin II on cyclooxygenase-2 (COX-2) expression in aortic adventitial fibroblasts from normotensive [Wistar-Kyoto (WKY)] rats and spontaneously hypertensive rats (SHRs). METHODS:Protein expression was determined by western blot, mRNA levels by real-time PCR, transcriptional...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/hjh.0b013e328317a730
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The screening for primary aldosteronism is based on the aldosterone-renin ratio calculated with the plasma renin activity (PRA) value as denominator. A direct measurement of active renin (DRA) is being used as an alternative to PRA, but its diagnostic performance remains unclear. METHOD:We, therefore compar...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32833d2192
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVES:The C825T single nucleotide polymorphism of the G-protein beta3 (GNB3) has been implicated in susceptibility to essential hypertension, through the expression of an alternatively spliced truncated variant. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based ...
journal_title:Journal of hypertension
pub_type: 杂志文章,meta分析
doi:10.1097/HJH.0b013e328011db24
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:To determine whether the noradrenergic sympathetic hyperinnervation in the spontaneously hypertensive rat (SHR), a genetic model of essential hypertension, is associated with changes in neurotrophin 3 (NT3) concentrations. METHODS:NT3 levels were measured using a sensitive enzyme-linked immunosorbent assay (...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200112000-00019
更新日期:2001-12-01 00:00:00
abstract:AIMS:Age-related increases in systemic blood flow [stroke volume (SV), cardiac output (CO), and aortic flow (Q)] contribute substantially to untreated or inadequately controlled (uncontrolled) blood pressure (BP) in Africa. We aimed to identify the haemodynamic determinants of uncontrolled systolic--diastolic (Syst--di...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002635
更新日期:2020-08-29 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:OBJECTIVE:To validate a computer-based method for measuring the calibre of retinal blood vessels, and use it to determine the effects of ageing and arterial hypertension on the calibres of these vessels and on their ratio. METHODS:Digital eye fundus images covering a 50 degrees field and centred on the optic disc were...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/01.hjh.0000163154.35577.8e
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND:Endogenous ouabain, an endogenous digitalis-like steroid, is synthesized in the adrenal glands and possibly in the hypothalamus. In vitro and in vivo, endogenous ouabain triggers growth and proliferation of cardiomyocytes. OBJECTIVE:We therefore investigated the association between left ventricular structur...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32832e49a8
更新日期:2009-09-01 00:00:00
abstract:OBJECTIVES:To assess the predictive role of changes in albuminuria on the loss of renal function under antihypertensive treatment in patients with type 2 diabetes (T2D). METHODS:Clinical records from a total of 12 611 patients with hypertension and T2D, attending 100 antidiabetic centers in Italy, with normal estimate...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001749
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Choice of antihypertensive drugs is also based on the expected burden of adverse events associated with each class of agents, and we have recently identified treatment discontinuation for adverse events as a measure of treatment tolerability frequently reported in randomized controlled trials (RCTs). OBJECT...
journal_title:Journal of hypertension
pub_type: 杂志文章,meta分析,评审
doi:10.1097/HJH.0000000000001052
更新日期:2016-10-01 00:00:00
abstract::Exogenous sex hormone use, including oral contraceptives, post-menopausal hormonal therapy and anabolic steroids, has been associated with blood pressure changes in both sexes, but little is known about the relationship between blood pressure and endogenous sex hormones. We examined this relationship in men in the Ran...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND:Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000179510.86265.63
更新日期:2005-10-01 00:00:00
abstract::The present study was designed to investigate in rats the influence of converting enzyme inhibition with captopril on blood pressure, plasma urea, plasma renin concentration (PRC), plasma aldosterone and plasma vasopressin, and to define the interrelationships between PRC and these variables during equal degrees of ei...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198604000-00008
更新日期:1986-04-01 00:00:00
abstract:OBJECTIVE:Studies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGN:The technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the co...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00