Abstract:
:Clopidogrel (CLO) is a clinical antiplatelet agent, about which there are major concerns because its antiplatelet efficiency decreases with insufficient metabolic activation, leading to "clopidogrel resistance." We aimed to determine the antiplatelet effects of W1, a novel molecule composed of 2-O-clopidogrel and aspirin (1:1 ratio), on platelet aggregation ex vivo and thrombus formation in vivo, and its susceptibility to CLO resistance in combination with other therapies in rats. Platelets were prepared, and an arteriovenous shunt thrombosis model was established using Wistar rats to measure platelet aggregation and thrombus formation, respectively. W1 markedly inhibited adenosine 5'-diphosphate (ADP)-induced platelet aggregation and thrombus formation dose dependently (0.3, 1, and 3 mg/kg). W1 (3 mg/kg) acted rapidly at 0.5 hours and lasted for 72 hours. W1 prolonged bleeding and clotting times in mice, confirming its antithrombotic properties. Compared with CLO 10 mg/kg, the positive control, W1 3 mg/kg exerted equivalent effects on the above specifications. In addition, cyclic adenosine monophosphate levels, measured in rat platelets, increased rapidly after prostaglandin E1 (alprostadil) stimulation of the vehicle control (0.5% methyl cellulose suspension) and W1 (3 mg/kg)-treated groups. ADP (50 μm) reduced the control levels more remarkably than W1 did (P < 0.05 in 3 minutes or P < 0.001 at 5 minutes), suggesting that W1 suppressed ADP-induced cyclic adenosine monophosphate reduction. This was associated with a significant platelet reactivity inhibition measured using the vasodilator-stimulated phosphoprotein assay. CLO or W1 coadministration with or without omeprazole and amlodipine to rats to investigate the pharmacodynamic interactions revealed that W1 exhibited more stable and potent antithrombotic effects than CLO did. In conclusion, both W1 and CLO showed antiplatelet and antithrombotic effects, while the former exhibited less CLO resistance in combination with omeprazole or amlodipine, 2 drugs that inhibit CLO metabolism. Therefore, this study implies that W1 may be a promising oral antiplatelet agent for reducing CLO resistance after percutaneous coronary intervention.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Ge P,Du L,Han C,Li H,Feng Y,Han J,Wang Z,Xiong L,Yuan M,Liu Ydoi
10.1097/FJC.0000000000000449subject
Has Abstractpub_date
2017-02-01 00:00:00pages
110-117issue
2eissn
0160-2446issn
1533-4023journal_volume
69pub_type
杂志文章abstract::Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myoca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31826216ed
更新日期:2012-10-01 00:00:00
abstract::It has been suggested that endothelin (ET) induces the release of endothelium-derived relaxing factor (EDRF). To explore the possible modification of ET-induced renal vasoconstriction by EDRF, we examined the effects of ET on renal vascular resistance (RVR) and urinary Na excretion (UNaV) in the rat isolated perfused ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00047
更新日期:1991-01-01 00:00:00
abstract::In a previous experiment, (-)-epigallocatechin-3-O-gallate (EGCG) reduced caffeine-induced locomotor activity and stereotyped behaviors and inhibited caffeine-induced neuronal stimulant activity. This research was performed to give additional evidence that EGCG counteracts caffeine-induced stimulant effects in animals...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0B013E31822D93CB
更新日期:2011-10-01 00:00:00
abstract::Endothelin (ET)-related peptides robustly stimulated [3H]-inositol phosphate (IP) formation in cultured cerebellar granule cells, astrocytes, and C6 glioma cells. Their agonist selectivities were ET-1 = ET-2 greater than or equal to sarafotoxin S6b greater than ET-3 greater than big ET-1 for granule cells and ET-1 gre...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::A randomized, double-blind, parallel-group study comparing the efficacy and tolerability of once-daily diltiazem capsules with amlodipine tablets in patients with stable angina. After a run-in period of 1 to 3 weeks, 34 patients received once-daily diltiazem and 33 patients received amlodipine. Patients received eithe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200109000-00004
更新日期:2001-09-01 00:00:00
abstract::We assessed the renal effects of moderate treadmill exercise in the spontaneously hypertensive rats (SHR) remnant kidney model of chronic renal failure (CRF). The effects of chronic administration of a specific endothelin (ET) subtype A (ETA) receptor antagonist, FR139317 (32 mg/kg/day i.p.) and an angiotensin-convert...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00139
更新日期:1998-01-01 00:00:00
abstract::Previous animal experiments suggest that the increase in the amplitude from the R-wave to the S-wave (RSh) may be more sensitive than other ECG measures to sodium channel blocking drug actions. We measured RSh of three orthogonal leads at baseline and during intravenous pharmacologic stimulation with adenosine, ajmali...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199510000-00023
更新日期:1995-10-01 00:00:00
abstract::Acetazolamide (ACTZ) vasodilating properties are used for the assessment of cerebral vasodilatory reserve not only in cerebral pathology investigation, but also in clinical pharmacology studies. However, the kinetics of these vasodilating properties are not clearly established; moreover, the cerebral selectivity of AC...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199511000-00022
更新日期:1995-11-01 00:00:00
abstract::To clarify the characteristics of KC-399, a newly synthesized potassium channel opener, we investigated the effects of KC-399 and lemakalim on the contractions induced by norepinephrine (NE 1 microM) and K+ (30 and 90 mM) and on 86Rb efflux in rat thoracic aorta. KC-399 (0.01-10 nM) and lemakalim (0.001-10 microM) ind...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::Meobentine (sulfate) has antifibrillatory and antiarrhythmic activity in canine models. The antiarrhythmic, pharmacokinetic, and adrenergic neuronal blocking effects of meobentine were assessed in 15 patients with chronic, high-frequency ventricular ectopic depolarizations (VEDs). Eleven of the 15 patients had recurre...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198407000-00015
更新日期:1984-07-01 00:00:00
abstract::During the last few years, there has been a growing awareness that treated hypertensive patients are still at substantially increased risks for cardiovascular morbidity and mortality and that one conceivable explanation for this is that their blood pressure has not been lowered to strictly normotensive levels. To obta...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198812006-00026
更新日期:1988-01-01 00:00:00
abstract::A dyshomeostasis of extra- and intracellular Ca(2+) and Zn(2+) occurs in rats receiving chronic aldosterone/salt treatment (ALDOST). Herein, we hypothesized that the dyshomeostasis of intracellular Ca(2+) and Zn(2+) is intrinsically coupled that alters the redox state of cardiac myocytes and mitochondria, with Ca(2+) ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181a15e77
更新日期:2009-05-01 00:00:00
abstract::Coronary artery disease is the most important cause of morbidity and mortality in Western countries. Its pathogenesis is unknown but involves an enhanced vasoconstriction and increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration, and extracellular matrix formation o...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1994-01-01 00:00:00
abstract::We established a real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) system for the analysis of rat endothelin-1 (ET-1) and vasoactive intestinal contractor (VIC)/ET-2 gene expression. We used this technique to examine the expression levels in rat in 16 different organs. ET-1 gene expressio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00004
更新日期:2000-11-01 00:00:00
abstract::The aim of the study was to compare the effects of atenolol (50 mg b.i.d.), verapamil (80 mg b.i.d.), xamoterol (200 mg b.i.d.), and matching placebo on heart rate (HR) and exercise tolerance in digitalised patients with chronic atrial fibrillation. Each treatment was taken for 4 weeks, and digoxin was continued throu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198901000-00002
更新日期:1989-01-01 00:00:00
abstract::Antihypertensive medications are the most efficient drugs in achieving regression of myocardial hypertrophy in both clinical studies and animal models of hypertension. Nevertheless, there is a lack of clear and concise comparative study of their effects on the modulation of cardiomyocyte morphology and function. Here,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000211728.23304.ad
更新日期:2006-04-01 00:00:00
abstract::Previously we showed that blocking the endothelin (ET)A receptor subtype with BQ-153 inhibited the vasoconstrictor effects of intravenously administered ET-1. In the presence of the ET(A) antagonist, ET-1 produced marked reductions in myocardial contractility and renal blood flow. We postulated that either the ET(B) r...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199706000-00002
更新日期:1997-06-01 00:00:00
abstract::It has previously been shown that endothelin (ET)-receptor antagonists protect the myocardium from ischemia and reperfusion (I/R) injury. The mechanism behind this effect is unclear. The aim of this study was to elucidate the possible interaction between ET(A)-receptor antagonism and nitric oxide (NO) during I/R. Anes...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200009000-00018
更新日期:2000-09-01 00:00:00
abstract::Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproduci...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:A diet rich in saturated fat and sugars (Western diet, WD) induces myocardial expression of the NLRP3 inflammasome and dysfunction in mice. We therefore hypothesized that a diet enriched with an orally available NLRP3 inflammasome inhibitor could prevent WD-induced cardiac dysfunction in mice. METHODS:Ten-w...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000628
更新日期:2018-12-01 00:00:00
abstract::Labedipinedilol-A is a novel 1, 4-dihydropyridine type calcium antagonist with alpha-receptor blocking activity. This study investigates the effects of labedipinedilol-A on mitogen-induced proliferation of rat vascular smooth muscle cells (VSMCs). Labedipinedilol-A's inhibition on cell proliferation was measured by th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200411000-00005
更新日期:2004-11-01 00:00:00
abstract::The present study examined the effects of central and peripheral administration of a vascular (V1) vasopressin (AVP) receptor antagonist on blood pressure, heart rate, and AVP levels in conscious rats. Rats subjected to rapid arterial haemorrhage were administered the AVP V1 antagonist [d(CH2)5Tyr(Me)AVP] either 5 min...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198810000-00005
更新日期:1988-10-01 00:00:00
abstract::Anakinra is a recombinant human interleukin 1 receptor antagonist that competes and blocks the biologic effects of interleukin 1, reducing systemic inflammatory responses. In the 2015 guidelines for the diagnosis and management of pericardial diseases of the European Society of Cardiology, anakinra was established as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000839
更新日期:2020-07-01 00:00:00
abstract::The pathogenic mechanism of nicotine, a major product of smoking, on vascular endothelial cells is not well defined yet. The purpose of this study was to determine whether chronic exposure to nicotine alters angiogenic activity in human umbilical vein endothelial cells and to identify a potential role for endothelial ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318206b5d9
更新日期:2011-03-01 00:00:00
abstract::The mechanisms of sustained ventricular tachycardia (VT) induced by large cumulative dose of cesium chloride (Cs) remains unclear. Seven anesthetized rabbits were intravenously injected with Cs (1 mmol/kg) 3 times at 20-min intervals. The surface ECG and monophasic action potential of the left ventricular endocardium ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199805000-00009
更新日期:1998-05-01 00:00:00
abstract:INTRODUCTION:We investigated the efficacy of carvedilol for preventing the recurrence of atrial fibrillation and reducing QT prolongation induced by bepridil. METHODS:We assigned 144 subjects with persistent atrial fibrillation. The subjects were divided into 3 groups: carvedilol plus bepridil, candesartan plus beprid...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3182790692
更新日期:2013-01-01 00:00:00
abstract::The vasoactive effects of calcium antagonist drugs were compared using a multi-organ functional imaging technique with thallium-201 (Tl-201). Four drugs were tested at two different doses: nifedipine (10 and 25 micrograms/kg), verapamil (100 and 250 micrograms/kg), diltiazem (100 and 250 micrograms/kg), and bepridil (...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198311000-00010
更新日期:1983-11-01 00:00:00
abstract::The oxidative modification of low-density lipoprotein (LDL) hypothesis implies that antioxidants should be effective in suppressing atherosclerosis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and irradiated hypercholesterolemic rabbits....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000179436.03502.26
更新日期:2005-10-01 00:00:00
abstract::The actions of prostacyclin and its synthetic analog iloprost on the release and action of platelet-derived serotonin (5-HT) and thromboxane (TX) A2 were studied in vitro. Washed human platelet suspensions (WPS) (4 X 10(8) platelets/ml) were stimulated with arachidonic acid (AA) (30 mumol/L) and the incubate transferr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198605000-00025
更新日期:1986-05-01 00:00:00
abstract::There has been some debate regarding the benefit of magnesium (Mg) in the treatment of acute myocardial infarction (AMI) because of conflicting results from recent clinical trials. Several different hypotheses have been advanced to explain the cardioprotective properties of Mg, including the influence of the timing of...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199612000-00012
更新日期:1996-12-01 00:00:00