Abstract:
:Endothelial dysfunction contributes to the initiation and development of hypertension. We previously found that simvastatin moderately decreases blood pressure in 2-kidney-2-clip (2k2c) renal hypertension, but the precise mechanisms are still unclear. The present study was designed to examine the protective actions of simvastatin in 2k2c-evoked endothelial dysfunction and also delineate the underlying mechanisms. Here we show that 2k2c-induced elevation in plasma angiotensin II impaired acetylcholine-induced endothelium-dependent vascular relaxation, suppressed endothelial NO synthase (eNOS) activity and reduced nitric oxide (NO) production. Additionally, the levels of tetrahydrobiopterin (BH4), an essential cofactor of eNOS, as well as the activity of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for BH4 synthesis, were markedly reduced. Administration of simvastatin significantly improved acetylcholine-induced endothelium-dependent carotid arteries relaxation at 9 weeks in reno-hypertensive rats. Notably, GTPCH I activity, BH4 production, p-eNOS expression and NO levels in the vascular endothelium were elevated as a result of simvastatin administration. In cultured rat arterial endothelial cells, simvastatin restored BH4, GTPCH I activity and NO release impaired by angiotensin II, and pretreatment with mevalonate (MVA) or geranylgeranyl pyrophosphate (GGPP) abolished the beneficial effects exerted by simvastatin. Moreover, RhoA inhibitor C3 exoenzyme, Rho kinase inhibitor Y-27632 and dominant negative mutant of RhoA prevented BH4 and NO loss due to Ang II treatment. Taken together, normalization of BH4-eNOS-NO pathway at least in part accounts for the beneficial actions of simvastatin on vascular endothelium during 2k2c hypertension, and RhoA-Rho kinase pathway is involved in regulation of BH4 production.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Zhang Z,Wang M,Xue SJ,Liu DH,Tang YBdoi
10.1007/s10557-011-6351-3subject
Has Abstractpub_date
2012-02-01 00:00:00pages
31-40issue
1eissn
0920-3206issn
1573-7241journal_volume
26pub_type
杂志文章abstract:INTRODUCTION:Irisin is a newly identified 112 amino acid hormone, derived as a product of fibronectin type III domain containing 5 (FNDC5), which is highly related to metabolic activity in skeletal muscle and brown fat. The effects of irisin on cardiovascular functions are unknown. PURPOSE:To explore the effects of ce...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6580-y
更新日期:2015-04-01 00:00:00
abstract::Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stu...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053555
更新日期:1991-10-01 00:00:00
abstract::A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, th...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01865507
更新日期:1989-08-01 00:00:00
abstract:PURPOSE:Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety. METHODS:The metabolic stability ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07129-z
更新日期:2021-01-07 00:00:00
abstract::As damage to the pulmonary vascular endothelium may be responsible for the lung toxicity of amiodarone, we evaluated the cytolytic toxicity of the drug in cultures of endothelial cells. Cells were cultured from human umbilical cord veins. Amiodarone caused a vacuolization of the cells with liberation of both lactate d...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00050996
更新日期:1996-11-01 00:00:00
abstract:PURPOSE:Protein kinase C alpha (gene: PRKCA) is a key regulator of cardiac contractility. Two genetic variants have recently been discovered to regulate PRKCA expression in failing human heart tissue (rs9909004 [T → C] and rs9303504 [C → G]). The association of those variants with clinical outcomes in patients with hea...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06909-6
更新日期:2019-12-01 00:00:00
abstract::Major advances have been established in the handling of hypertensive vascular disease in recent years. However, drug compliance, drug costs, and the side effects of antihypertensive agents have prompted the question of whether intermittent therapy or even possible removal of medication represents an alternative to lif...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02026496
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVE:The aim was to study the pharmacodynamic interactions and safety of the co-administration of the calcium sensitizer levosimendan and the calcium antagonist felodipine in patients with coronary heart disease (CHD) and with normal ejection fraction (EF). METHODS:The study was a randomized, double blind, placeb...
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/b:card.0000015860.08185.6d
更新日期:2003-09-01 00:00:00
abstract::Calcium entry blockers exert several characteristic effects on renal function that contribute to their blood-pressure lowering capacity. They are able to dilate renal vasculature and, in certain circumstances, can increase the glomerular filtration rate, both effects being dependent on the preexisting vascular tone. C...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02018304
更新日期:1990-08-01 00:00:00
abstract::Tracer techniques have provided new insight in cardiology by allowing noninvasive studies of myocardial perfusion, function, metabolism, and, more recently, ligand-receptor interaction. Positron emission tomography allows accurate quantification and the use of natural substrates labelled with 11C, 13N, or 15O. Myocard...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00051291
更新日期:1990-08-01 00:00:00
abstract::The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coro...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01856557
更新日期:1990-06-01 00:00:00
abstract:PURPOSE:To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients. METHODS:We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07133-3
更新日期:2021-01-04 00:00:00
abstract::Obesity is one of the most common lifestyle-related diseases. Being closely associated with insulin resistance, hypertension and dyslipidemia, it is also a component of metabolic syndrome and is involved in the development of atherosclerosis and cardiovascular and renal ailments. Obesity is also accompanied with a sta...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-011-6335-3
更新日期:2011-10-01 00:00:00
abstract::Recent studies have questioned the safety of calcium antagonists in general, and short-acting dihydropyridine derivatives in particular. Reasons include excessive catecholamine stimulation after stress. We therefore wanted to assess whether amlodipine, a second generation dihydropyridine with a prolonged plasma half-l...
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:1007875603969
更新日期:1999-11-01 00:00:00
abstract::The aim of this study was to compare the pharmacokinetics and antiarrhythmic activity of dihydroquinidine and quinidine in 14 patients (11 men, 3 women, aged 28 to 67 years) with heart disease and chronic, stable, high-frequency premature ventricular beats (PVB) (greater than 100/hr). A randomized, double-blind, cross...
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/BF00054209
更新日期:1988-12-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the efficacy and safety of intravenous infusion of low-dose flecainide (50 mg) followed by oral pilsicainide (50 mg t.i.d.)in patients with paroxysmal atrial fibrillation (AF). METHODS:Thirty-one patients with symptomatic and hemodynamically stable AF lasting less than 48 ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,信件
doi:10.1023/a:1024368111557
更新日期:2003-01-01 00:00:00
abstract::Ranolazine, an inhibitor of the late current of the cardiac action potential (late I(Na)), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-014-6548-3
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na (+) current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazin...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6587-4
更新日期:2015-06-01 00:00:00
abstract::Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877091
更新日期:1994-02-01 00:00:00
abstract::Concentrations of the circulating hepatocyte growth factor (HGF) increase in the very early phase of acute myocardial infarction, and are a marker of arterial thrombosis. A recently developed, highly sensitive HGF assay can detect the early stages of arterial thrombosis in patients with unstable angina pectoris, acute...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/B:CARD.0000041252.33870.74
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS:We examined the prevalence and outcomes associated...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6754-x
更新日期:2017-12-01 00:00:00
abstract::Though the exact physiology and pathology of lipoprotein(a) [Lp(a)] remains unknown, it has been demonstrated that increased serum Lp(a) levels are correlated with an increased risk of atherosclerotic vascular disease. The effects of lipid-lowering drugs on Lp(a) levels is unclear because of inconsistencies between st...
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:10.1007/BF00878550
更新日期:1995-10-01 00:00:00
abstract::Resistance arteries depolarize and constrict to elevations in intravascular pressure. However, many of the molecular aspects of this phenomenon are not known. We present evidence that large conductance calcium-dependent potassium (KCa) channels, which are activated by intracellular calcium and membrane depolarization,...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877627
更新日期:1993-08-01 00:00:00
abstract::Diuretics, either as monotherapy or in combination with other drugs in the management of hypertension, have retarded the development of left ventricular hypertrophy and congestive heart failure in many patients. Diuretics also remain one of the most effective therapies in the treatment of congestive heart failure, whe...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1007791814100
更新日期:1997-05-01 00:00:00
abstract::In two separate, double-blind, multicenter antiarrhythmic studies, sotalol was compared with propranolol or quinidine using placebo for baseline and/or washout periods. The comparison with quinidine was a crossover study. To be enrolled in these studies, patients were required to have a premature ventricular contracti...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00357038
更新日期:1990-06-01 00:00:00
abstract::The hypothesis tested was that enhanced entry of calcium into cardiac cells would increase the susceptibility to ventricular fibrillation as measured by the ventricular fibrillation threshold (VFT) of the isolated perfused rat heart. Bay-K-8644 was used as a calcium-channel agonist. There was a biphasic effect with a ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00052561
更新日期:1992-12-01 00:00:00
abstract:INTRODUCTION:Surrogate markers represent a significant contribution to early diagnosis, longitudinal prognoses, and outcome prediction in cases of hypertension. They often enable detection of disease and disease potential when the disease is still subclinical and are useful noninvasive tools for designing and evaluatin...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-009-6177-4
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting. METHODS:Male non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induc...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-06954-6
更新日期:2020-06-01 00:00:00
abstract::Inhibition of the renin-angiotensin system has been a highly successful therapeutic approach for the prevention of hypertension-related end organ damage. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers lower blood pressure and reduce morbidity and mortality in patients with cardiovascular...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-010-6278-0
更新日期:2011-02-01 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