Abstract:
AIMS:Therapeutic use of sulfhydrylated inhibitor S-zofenopril has raised different hypotheses regarding the role played by its thiol group in the beneficial clinical effects exerted compared with other angiotensin-converting enzyme (ACE) inhibitors. Here, we investigated hydrogen sulfide (H2S) pathway as accountable for extra-beneficial effects in vascular function. METHODS AND RESULTS:Spontaneously hypertensive rat (SHRs) and control Wistar Kyoto (WKY) rats were treated with either S-zofenopril or enalapril in vivo. Aorta and carotid were harvested and ex vivo vascular reactivity to acetylcholine (Ach) and L-cysteine (L-cys) assessed. Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptosulfur-transferase (3MST) expression, as well as H2S levels, were evaluated in both vascular tissues. The vascular response to Ach in both carotid and aorta was impaired in SHR (~30%, P < 0.001). S-zofenopril, but not enalapril, restored this response, while L-cys-induced relaxation was enhanced. CSE expression in vessels and tissue/plasma H2S levels were restored to WKY values in SHRs receiving S-zofenopril. In contrast, CBS and 3MST expression were not modified by treatments. S-zofenoprilat, an active metabolite of S-zofenopril, releases H2S in a 'cell-free' assay and it directly relaxed vessels in vitro in a concentration-dependent manner (P < 0.001). In vivo administration of R-zofenoprilat diasteroisomer, which does not inhibit ACE, did not modify blood pressure; nonetheless, it retained the beneficial effect on SHR vascular function as well as restored plasma/tissue H2S levels. CONCLUSION:Our findings establish that S-zofenopril improves vascular function by potentiating the H2S pathway in a model of spontaneous hypertension. This novel mechanism, unrelated to ACE inhibition and based on H2S release, could explain the beneficial effects of sulfhydrylated ACE inhibitors reported in the clinical literature.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Bucci M,Vellecco V,Cantalupo A,Brancaleone V,Zhou Z,Evangelista S,Calderone V,Papapetropoulos A,Cirino Gdoi
10.1093/cvr/cvu026subject
Has Abstractpub_date
2014-04-01 00:00:00pages
138-47issue
1eissn
0008-6363issn
1755-3245pii
cvu026journal_volume
102pub_type
杂志文章abstract::Microelectrode recordings of skin nerve sympathetic activity were made in the median nerve supplying the right hand of nine patients with Raynaud's phenomenon and 10 control subjects. With subjects warmed up (finger temperature 33 to 34 degrees C) different manoeuvres were used to evoke strong, single sympathetic burs...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.5.249
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:Although aldosterone has been implicated in the pathogenesis of cardiac hypertrophy and heart failure, its cellular mechanism of action on cardiomyocyte function is not yet completely elucidated. This study was designed to investigate the effect of aldosterone on calcium channel expression and cardiomyocyte c...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.009
更新日期:2005-08-01 00:00:00
abstract:OBJECTIVE:Insulin protects cardiomyocytes from apoptosis. Insulin resistance usually refers to a defect in the ability of insulin to stimulate glucose uptake. It is unknown, however, whether or not insulin resistance compromises the cell-protective effect of the hormone. Caspases are a family of cysteine proteases that...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.07.012
更新日期:2007-12-01 00:00:00
abstract:OBJECTIVE:The aim was to assess the significance of polymorphonuclear leucocytes on the myocardial capillary permeability to a small hydrophilic indicator, on the vascular tone of the resistance vessels, and on contractile function following ischaemia and reperfusion. METHODS:Open chest, anaesthetised dogs were random...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.7.1288
更新日期:1993-07-01 00:00:00
abstract:OBJECTIVE:Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS:To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00278-4
更新日期:2001-07-01 00:00:00
abstract::CaMKII is a serine-threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflamm...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw002
更新日期:2016-04-01 00:00:00
abstract::Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs de...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.12.711
更新日期:1981-12-01 00:00:00
abstract:Aims:β1-adrenergic receptor autoantibodies (β1-AAs) and β2-adrenergic receptor autoantibodies (β2-AAs) are present in patients with heart failure (HF); however, their interrelationship with cardiac structure and function remains unknown. This study explored the effects of the imbalance between β1-AAs and β2-AAs on card...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy105
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+(ATP)) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+(ATP) channels. METHODS:Guinea pig ventricular myocytes were isolated using collagenase digestion....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00092-8
更新日期:1997-08-01 00:00:00
abstract:OBJECTIVES:Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Bloo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.12.734
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND:Plasma low density lipoproteins (LDL) play a key role in the pathogenesis of atherosclerosis. LDL modify gene expression in vascular cells leading to disturbances in the functional state of the vessel wall. METHODS:Expression levels of C-4 sterol methyl oxidase gene (ERG25), sterol regulatory element bindin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00856-8
更新日期:2003-04-01 00:00:00
abstract:AIMS:Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:Mice ...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt235
更新日期:2014-01-01 00:00:00
abstract::End-diastolic current thresholds have been measured in 12 open-chested dogs with epicardial disc electrodes ranging in radius from 0.01 to 9.0 mm. The current threshold for cathodal 1 ms impulses proved to be independent of electrode size for radii smaller than 0.2 mm and proportional to the radius to the power 1.5 fo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.8.477
更新日期:1978-08-01 00:00:00
abstract:AIMS:Germ-line mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) pathway cause developmental disorders called RASopathies. Hypertrophic cardiomyopathy (HCM) is the most common myocardial pathology and a leading cause of death in RASopathy patients. KRAS mutations are found in Noo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt260
更新日期:2014-02-01 00:00:00
abstract::Surgical preparation of human saphenous vein for coronary artery bypass grafting involving distension and storage in iso-osmotic sodium chloride solution reduced tissue adenosine triphosphate (ATP) (mean(SEM] concentration from 280(20) nmol.g-1 wet wt (n = 25) to 140(30) nmol.g-1 wet wt (n = 12) and the adenosine trip...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.12.902
更新日期:1987-12-01 00:00:00
abstract:OBJECTIVE:In human heart failure beta-adrenergic-mediated protein kinase A (PKA) activity is down-regulated, while protein kinase C (PKC) activity is up-regulated. PKC-mediated myofilament protein phosphorylation might be detrimental for contractile function in cardiomyopathy. This study was designed to reveal the effe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.11.021
更新日期:2006-03-01 00:00:00
abstract::Experimental studies have provided evidence that the autonomic nervous activity is modulated by oestrogen. Such modulation at central and peripheral levels tends to suppress sympathetic but elevate parasympathetic tone to the cardiovascular system. Thus, available data support the view that cardiovascular protection b...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:
更新日期:1995-08-01 00:00:00
abstract:AIMS:The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw233
更新日期:2017-01-01 00:00:00
abstract:AIMS:Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood. METHODS AND RESUL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq353
更新日期:2011-04-01 00:00:00
abstract::The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.7.536
更新日期:1986-07-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to record diastolic transmitral pressure gradients at high sensitivity to quantitate the effect on transmitral pressure gradients of changing the heart rate. DESIGN:Diastolic left atrial and left ventricular pressures were recorded at high sensitivity (40 mm Hg = 10 mm recorded deflection) ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.7.560
更新日期:1990-07-01 00:00:00
abstract:OBJECTIVE:Catechol O-methyltransferase (COMT) is believed to exert degradative action at high norepinephrine (NE) levels. Although COMT exists in cardiac tissues, the contribution of cardiac COMT activity to regional NE kinetics, particularly in ischemia-induced NE accumulation, remains unclear. We investigated the rol...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.06.011
更新日期:2004-10-01 00:00:00
abstract::Vasculopathy is a pathological process occurring in the blood vessel wall, which could affect the haemostasis and physiological functions of all the vital tissues/organs and is one of the main underlying causes for a variety of human diseases including cardiovascular diseases. Current pharmacological interventions aim...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa313
更新日期:2020-11-02 00:00:00
abstract::Labetolol, which blocks both alpha and beta-adrenoceptors, was found to have direct actions on cardiac muscle which could themselves be antiarrhythmic. It depressed the maximum rate of depolarisation, and reduced conduction velocity, in atrial and ventricular muscle and in Purkinje cells, implying restriction of fast ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.5.233
更新日期:1982-05-01 00:00:00
abstract:AIMS:The regulation of vascular diameter by vasoconstrictors and vasodilators requires that vascular smooth muscle cells (VSMCs) be physically coupled to extracellular matrix (ECM) and neighbouring cells in order for a vessel to mechanically function and transfer force. The hypothesis was tested that integrin-mediated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs239
更新日期:2012-10-01 00:00:00
abstract::The effect of lidocaine on the effective refractory period of the right ventricle (EVRP) was measured in 10 patients using the extra stimulus technique of progressive introduction of premature stimuli until a response could not be elicited. In four patients lidocaine produced a significant decrease in the EVRP, in a f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.5.621
更新日期:1975-09-01 00:00:00
abstract::The effects of hypoxia and subsequent reoxygenation were examined in isolated left ventricular papillary muscles from the rat at 28 degrees C and 33 degrees C. Studies of relaxation were carried out in isometric and physiologically sequenced contractions. In studies of isometric contractions, the following variables w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.9.690
更新日期:1986-09-01 00:00:00
abstract:OBJECTIVES:Injury stimulates smooth muscle cell (SMC) migration and proliferation by mechanisms that are incompletely understood. Surgical preparative injury is an important determinant of neointimal thickening in human saphenous vein bypass grafts. We investigate here whether basement-membrane-degrading metalloprotein...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00211-8
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate whether infusion of either atrial natriuretic factor (ANF, 800 ng.h-1.rat-1) or a specific inhibitory of neutral endopeptidase 24.11 (NEI, UK 73,967, 5.4 mg.kg-1.d-1) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia. METHODS:Male Wist...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.4.519
更新日期:1994-04-01 00:00:00