Abstract:
:Cilazapril, an angiotensin-converting enzyme inhibitor, and mibefradil, a selective T-type voltage-operated calcium channel blocker, have been shown to prevent neointima formation after vascular injury. The goal of the present study was to evaluate the mechanism of action of both drugs. For this purpose, the influence of the renin angiotensin system on the effects of mibefradil (30 mg/kg po) and cilazapril (10 mg/kg po) on neointima formation after carotid injury were evaluated in normotensive rats (normal renin angiotensin system) and DOCA hypertensive rats (suppressed renin angiotensin system). In addition, in order to differentiate an effect on cell migration or cell proliferation, both drugs were given either before or after the smooth muscle migration phase. Finally, cilazapril and mibefradil were given in combination. In normotensive rats, mibefradil and cilazapril decreased neointima formation, resulting in neointima/media ratios of 38% (p < 0.05) and 53% (p < 0.01), respectively. However, in DOCA hypertensive rats, mibefradil was active, with a reduction of the neointima/media ratio by 63% (p < 0.001), whereas cilazapril reduced it only slightly (19%) and not significantly. In addition, cilazapril was active only when treatment started before the migration phase (63%, reduction in neointima/media ratio, p < 0.001) but not when started thereafter (13% reduction in neointima/media ratio, n.s.). In contrast, treatment with mibefradil was also active when started after the migration phase (51% reduction in neointima/ media ratio, p < 0.001 when treatment started 1 day before balloon injury and 41%, p < 0.01 when treatment started 5 days after balloon injury). The combination of both drugs was additive (67% reduction in neointima/media ratio, p < 0.001 vs. control). These experiments clearly show that mibefradil and cilazapril have a different mechanism of action after vascular injury. Mibefradil most likely prevents the proliferation of smooth muscle cells. In contrast, cilazapril most likely inhibits the migration of smooth muscle cells. These two different mechanisms of action explain why the effects of both drugs are additive.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Schmitt R,Clozel JP,Iberg N,Bühler FRdoi
10.1007/BF00823586subject
Has Abstractpub_date
1996-05-01 00:00:00pages
101-5issue
2eissn
0920-3206issn
1573-7241journal_volume
10pub_type
杂志文章abstract::A succession of theories arising from last century has attempted to explain why patients with damaged hearts develop peripheral edema. Opposed to the original simple concepts of backward failure, a number of theories of forward failure have been proposed, the cardiac output being considered inadequate for capillary pe...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877921
更新日期:1994-06-01 00:00:00
abstract::Mitochondrial health is critically dependent on the ability of mitochondria to undergo changes in mitochondrial morphology, a process which is regulated by mitochondrial shaping proteins. Mitochondria undergo fission to generate fragmented discrete organelles, a process which is mediated by the mitochondrial fission p...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-016-6710-1
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abstract::To assess the effect of antihypertensive drugs on aortic distensibility, we evaluated the aortic distensibility of 33 hypertensive patients before and after antihypertensive treatment by using cine magnetic resonance imaging. Thirty three hypertensive patients were divided into three groups and treated for 12 weeks wi...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1007711617112
更新日期:1999-07-01 00:00:00
abstract::We studied the acute and chronic effects of propionyl-L-carnitine (PLC) on mechanical function of isolated rabbit heart. Propionyl-L-carnitine was either directly delivered in the perfusate (10(-9) to 10(-3) M) or intraperitoneally injected (250 mg/kg) for 10 days to the animals. When added acutely, propionyl-L-carnit...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00128239
更新日期:1991-02-01 00:00:00
abstract:PURPOSE:Treatment of pulmonary arterial hypertension (PAH) by vasodilator drug monotherapy is often limited in its effectiveness. Combination therapy may help to improve treatment and to reduce drug toxicity. This study assessed the combination of the endothelin receptor antagonist macitentan and the phosphodiesterase-...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06868-y
更新日期:2019-06-01 00:00:00
abstract::Left ventricular dysfunction is in most cases the consequence of myocardial ischemia. It may occur transiently during an attack of angina and usually it is reversible. It may persist over hours or even days in patients after an episode of ischemia followed by reperfusion, leading to the so-called condition of stunning...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877322
更新日期:1994-05-01 00:00:00
abstract:PURPOSE:Although the role of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension has been well established, no data has been generated regarding the influence of ACE inhibitors for health-related quality-of-life (QOL) dimensions for Chinese patients. MATERIALS:A double-blind, active-contro...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1020648405680
更新日期:2002-05-01 00:00:00
abstract::Recent surveys in the U.S. have reported, for the first time, that a significant number of patients with hypertension are finding that the cost of medication and treatment in general is an obstacle to treatment. The cost of management of hypertension can be contained if: a) the diagnostic workup is kept simple (this d...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01857624
更新日期:1989-10-01 00:00:00
abstract::Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, C...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-016-6677-y
更新日期:2016-08-01 00:00:00
abstract::The majority of calcium antagonists used clinically belong to three distinct chemical classes: the phenylalkylamines, the dihydropyridines, and the benzothiazepines. In recent years their mode of action has been unravelled, their limitations recognized, and their efficacy and use in the management of patients with a b...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877225
更新日期:1994-08-01 00:00:00
abstract::Chronic renal failure (CRF) patients with a stable course were asked to participate in a follow-up program in which they were randomized into two groups: 1) the placebo group taking their standard antihypertensive therapy without any calcium ion blocker: and 2) the nisoldipine group, those patients taking the calcium ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02125735
更新日期:1988-01-01 00:00:00
abstract::Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174....
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF00877120
更新日期:1994-10-01 00:00:00
abstract:PURPOSE:The progressive shortening of the atrial effective refractory period (ERP) during atrial fibrillation (AF) might be due to the activation of the KATP channels by rapid atrial rates. We tested the hypothesis that the cardioselective, sarcolemmal KATP channel blocker HMR 1098 would prevent atrial ERP shortening d...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/B:CARD.0000025752.63337.b2
更新日期:2004-01-01 00:00:00
abstract::Beta-blocker-induced benefit in heart failure is under intense evaluation. Several large-scale mortality trials are currently being performed, with CIBIS II evaluating bisoprolol. The economic impact of beta-blocker therapy in heart failure has not been previously determined. The present study is a cost-effectiveness ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1007773901631
更新日期:1998-07-01 00:00:00
abstract::In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequelae in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post-hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHE...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1007891121240
更新日期:2000-02-01 00:00:00
abstract::Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha-toc...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF00054753
更新日期:1991-03-01 00:00:00
abstract::High-density lipoprotein cholesterol (HDL-c) has long been referred to as 'good cholesterol' due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled t...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-018-06846-w
更新日期:2019-04-01 00:00:00
abstract:OBJECTIVE:This review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage. METHODS:Randomized controlled trials of CRT in patients with New York Heart Association (NYHA...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s10557-011-6313-9
更新日期:2011-08-01 00:00:00
abstract::Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120497
更新日期:1996-06-01 00:00:00
abstract:PURPOSE:Although erythropoietin (EPO) is known to express angiogenic and cardioprotective effects, it also induces hypertension, polycythemia, and platelet activation, which may cause serious adverse effects in patients with cardiovascular diseases. We compared the angiogenic effects of EPO and its nonerythropoietic de...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-013-6438-0
更新日期:2013-04-01 00:00:00
abstract::The use of calcium antagonists and diuretics in combination for treatment of hypertension is controversial. In a single-blind study 16 patients (8 men, 8 women, age range 39 to 62 years) with primary hypertension of mild to moderate degree were given slow-release nifedipine 20 mg twice daily for 6 weeks, thereafter ei...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02125751
更新日期:1988-03-01 00:00:00
abstract:PURPOSE:Epidemiologic and clinical research suggests important gender-related differences in the prevalence, presentation, associated conventional and non-conventional risk factors, management and outcomes of coronary heart disease (CHD) patients. Adequate data is not available for Indian population where prevalence of...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6594-5
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:High health service expenditure on the one hand, and the politically declared objective of stability of statutory contributions and restriction of public funds on the other hand, have been central points of the political and social discussion for several years. The over-proportional increase in health servic...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1015323700206
更新日期:2002-01-01 00:00:00
abstract::This review will present a summary of a description of apoptotic pathways in the heart, followed by ways to measure it and the experimental and clinical evidence for the role of apoptosis in cardiac disease. An evaluation of the effectiveness of pharmacological and other therapeutic interventions in the prevention of ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1013715704835
更新日期:2001-11-01 00:00:00
abstract:INTRODUCTION:Several beta blocking drugs (BB) reduce mortality in systolic heart failure (LVSD). We have compared the initial response to introduction of carvedilol and bisoprolol during the standard dose titration protocols for each drug. METHODS:Approximately 31 unselected patients with stable LVSD were randomised t...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10557-007-6055-x
更新日期:2007-12-01 00:00:00
abstract::There can be no doubt that ACE inhibitors prolong survival in patients with a low ejection fraction. There is no evidence whether or not diuretics have the same effect. The pathophysiology of asymptomatic patients with poor left ventricular function differs from that of patients with the clinical syndrome of heart fai...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877716
更新日期:1993-12-01 00:00:00
abstract:INTRODUCTION:Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications for anti-arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated the electrophysiological effects of three di...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6001-y
更新日期:2007-02-01 00:00:00
abstract::Cardiovascular disease is the leading cause of death in men and women in the USA. Once a patient experiences an acute coronary syndrome (ACS), they are at increased risk for hospital readmission within 30 days and 6 months after discharge and more importantly, they have worse survival. Hospital readmissions lead to po...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-018-6798-6
更新日期:2018-12-01 00:00:00
abstract::Although torsades de pointes is not a tightly demarcated entity, the diagnosis has important clinical implications. The concept should be retained. ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029821
更新日期:1991-02-01 00:00:00
abstract::In order to compare and clarify the effects of various antiarrhythmic drugs when given as monotherapy, we reevaluated our previous data on antiarrhythmic drugs and recalculated antiarrhythmic plasma concentrations of drugs for several canine arrhythmia models. We used three spontaneously occurring arrhythmias: a) digi...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120829
更新日期:1991-08-01 00:00:00