Abstract:
PURPOSE:We tested if inhibition of phosphodiesterases (PDEs) with IBMX (1-methyl-3-isobutylxanthine) can modulate the mitochondrial permeability transition pore (mPTP) opening by inactivating glycogen synthase kinase 3β (GSK-3β). METHODS:H9c2 cells were exposed to 600 μM H(2)O(2) for 20 min to cause the mPTP opening. Mitochondrial membrane potential (ΔΨm) was assessed by imaging cells loaded with tetramethylrhodamine ethyl ester (TMRE). Cell viability was measured with propidium iodide (PI) fluorometry using a fluorescence reader. Ischemia/reperfusion injury was induced by exposing cells to ischemic solution for 90 min followed by 30 min of reperfusion. RESULTS:IBMX reduced loss of ΔΨm caused by H(2)O(2), indicating that inhibition of PDEs can prevent the mPTP opening. However, IBMX could not inhibit the pore opening in cells transfected with the constitutively active GSK-3β (GSK-3β-S9A) mutant, suggesting a critical role of GSK-3β in the action of IBMX. IBMX also reduced reperfusion injury in a GSK-3β dependent manner. In support, IBMX increased GSK-3β phosphorylation at Ser(9), an effect that was reversed by both the PKA inhibitor H89 and the PKG inhibitor KT5823. In support, IBMX activated both PKA and PKG. IBMX failed to prevent the loss of ΔΨm in the presence of H89 or PKA siRNA. Similarly, both KT5823 and PKG siRNA reversed the protective effect of IBMX. CONCLUSION:Inhibition of PDEs prevents the mPTP opening by inactivating GSK-3β through PKA and PKG. GSK-3β is a common downstream target of PKA and PKG. Inhibition of PDEs may be a useful approach to prevent reperfusion injury.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Chanoit G,Zhou J,Lee S,McIntosh R,Shen X,Zvara DA,Xu Zdoi
10.1007/s10557-011-6310-zsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
299-306issue
4eissn
0920-3206issn
1573-7241journal_volume
25pub_type
杂志文章abstract::The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experimen...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00143532
更新日期:1991-12-01 00:00:00
abstract::Based on a retrospective analysis of the DAVIT II database, we attempted to propose subgroups of post-infarction patients with heart failure, who might benefit or not benefit from antiischemic medical intervention. In DAVIT II, patients were randomized in a double-blind fashion to either verapamil 360 mg/day or placeb...
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/BF00877400
更新日期:1994-12-01 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::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::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::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::The following discourse addresses the pharmacologic profile of KT-362, its clinical potential as an anti-arrhythmic agent with associated hypotensive effects, as well as its additional related potential in myocardial ischemia and related sequellae, and the specific cellular actions that may be responsible for these po...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02018262
更新日期:1990-10-01 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::In vitro and in vivo studies have demonstrated many similarities between the three calcium antagonists verapamil, nifedipine, and diltiazem in relation to protection of the myocardium during hypoxia. Important clinical differences exist between the three drugs when they are used during or after an acute myocardial inf...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF03029738
更新日期:1991-08-01 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::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::Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on...
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/BF02627961
更新日期:1996-07-01 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::One hundred thirteen patients undergoing cardiopulmonary bypass were randomly assigned to receive either bovine or porcine heparin. Heparin was infused at 4.5 mg/kg during bypass and administered at the lesser of 70 units/kg or 5000 units/dose at 12-hour intervals postoperatively. Platelet counts decreased to 45% of p...
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/BF01857644
更新日期:1990-02-01 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::Blood pressure is controlled by many factors, and thus hypertension is a multifactorial disorder. This etiologic diversity is also reflected in the broad spectrum of different pharmacologic agents known to lower blood pressure. Most carefully controlled studies employing a single antihypertensive drug in unselected, u...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02603180
更新日期:1990-03-01 00:00:00
abstract:PURPOSE:The mitogen-activated protein kinase phosphatases (MKPs) are a family of dual-specificity phosphatases that inactivate MAPKs by dephosphorylation. Impairment of MKP-1 expression in insulin resistance has been suggested to affect the cardioprotective properties of insulin. We hypothesized that manipulation of it...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6731-4
更新日期:2017-06-01 00:00:00
abstract::When severely ischemic myocardium is reperfused, prolonged myocardial dysfunction--a phenomenon named myocardial stunning--frequently occurs. Stunning also occurs in a variety of other situations. These include myocardium located adjacent to infarcted tissue, transient increase in myocardial O2 demands in the presence...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053546
更新日期:1991-10-01 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::With the increased use of long-acting nitroglycerin preparations, there has been greater recognition of the problem of nitrate tolerance. In recent years extensive research has broadened our understanding of the mechanisms of nitroglycerin action and the mechanisms of drug attenuation. This paper reviews the current s...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01857640
更新日期:1990-02-01 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:AIMS:We evaluated a generic quality of life (QoL) Functional Status Questionnaire (FSQ), in patients with chronic heart failure (CHF). The FSQ assesses the 3 main dimensions of QoL: physical functioning, mental health and social role. It also includes 6 single item questions about: work status, frequency of social inte...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10557-011-6284-x
更新日期:2011-02-01 00:00:00
abstract::Despite the impressive relation between an increased blood cholesterol and increased mortality from coronary artery disease and despite the persuasive results of cholesterol-lowering trials in secondary prevention, there are increasing reservations about the wisdom of lowering moderately raised blood cholesterol level...
journal_title:Cardiovascular drugs and therapy
pub_type: 社论
doi:10.1007/BF00878930
更新日期:1993-11-01 00:00:00
abstract:PURPOSE:Ranolazine (RAN) added to amiodarone (AMIO) has been shown to accelerate termination of postoperative atrial fibrillation (POAF) following coronary artery bypass surgery in patients without heart failure (HF). This study aimed to investigate if treatment efficacy with AMIO or AMIO + RAN differs between patients...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10557-018-6832-8
更新日期:2018-12-01 00:00:00
abstract::The effects of short- and long-term administration of nifedipine on serum lipids, lipoproteins, and apolipoproteins (apo) were studied. Administration of nifedipine capsule for 4 months significantly decreased triglycerides and increased the HDL2 cholesterol and the HDL2/HDL3 cholesterol ratio. No significant changes ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF02018313
更新日期:1990-08-01 00:00:00
abstract::The combination of aspirin and clopidogrel is the mainstay antiplatelet therapy for acute coronary syndromes (ACS). However, the dosing of aspirin, the dosing of clopidogrel, the timing of clopidogrel initiation as well as the duration of clopidogrel therapy remain controversial matters. Clopidogrel resistance is an e...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-009-6212-5
更新日期:2010-02-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstric...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-015-6605-6
更新日期:2015-01-01 00:00:00
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::Thrombolytic therapy has gained widespread acceptance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfus...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00133206
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Azelnidipine is a novel dihydropyridine calcium channel blocker. Several studies have demonstrated that some dihydropyridine calcium channel blockers have antioxidant effects. We evaluated the antioxidant effects of azelnid...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6008-4
更新日期:2007-02-01 00:00:00