Abstract：
:Endothelial damage triggers platelet adhesion and platelet-associated prothrombinase formation at the point of injury, resulting in the progression of thrombus formation. The present study compared the inhibitory effects of fondaparinux, an indirect factor Xa (FXa) inhibitor, and TAK-442, a direct FXa inhibitor, on platelet-associated prothrombinase activity in the balloon-injured rat artery. TAK-442 and fondaparinux inhibited endogenous FXa activity in platelet-poor human [half-maximal inhibitory concentration (IC(50)): 53 nM, TAK-442; 11 nM, fondaparinux] and rat (IC(50): 32 nM, TAK-442; 19 nM, fondaparinux) plasma. TAK-442 inhibited in vitro reconstituted human prothrombinase (system included FXa, calcium, and washed platelets) with an IC(50) value of 51 nM, whereas fondaparinux exhibited only weak inhibition (IC(50): 1700 nM). In a rat model of balloon injury, thrombin activity on the surface of injured vessels increased to 3.2-, 22-, and 5.8-fold the activity on the surface of the intact aorta at 5 minutes, 1 hour, and 24 hours after the injury, respectively. At approximately 1 hour after the injury, TAK-442 blocked platelet-associated thrombin generation on the surface of injured aortas with an IC(50) value of 19 nM, whereas fondaparinux showed no significant inhibition at the highest concentration tested (IC(50): >300 nM). These results suggest a possible limitation of fondaparinux in inhibiting platelet-associated prothrombinase activity and resultant thrombus formation as compared with TAK-442.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Konishi N,Hiroe K,Kawamura Mdoi
10.1097/FJC.0b013e31820382a9subject
Has Abstractpub_date
2011-02-01 00:00:00pages
201-6issue
2eissn
0160-2446issn
1533-4023journal_volume
57pub_type
杂志文章abstract：:The mechanism by which nicotine causes peripheral vasoconstriction and its relationship to the increased risk of peripheral vascular disease in smokers are unknown. To study the peripheral vascular effects of nicotine, we measured hemodynamic responses and oxygen consumption of the in situ gracilis muscle during intra...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199110000-00009
更新日期：1991-10-01 00:00:00
abstract：:Bay k 8644, a new dihydropyridine calcium channel activator has been shown to have positive inotropic and vasoconstrictor properties following intravenous (i.v.) administration. In the present study, intracoronary administration of Bay k 8644 was used to isolate drug effects on regional myocardial blood flow and contr...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198611000-00019
更新日期：1986-11-01 00:00:00
abstract：:The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group....
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199007000-00012
更新日期：1990-07-01 00:00:00
abstract：:Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated i...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199802000-00004
更新日期：1998-02-01 00:00:00
abstract：:Left ventricular hypertrophy (LVH), an increase in the muscle mass of the left ventricle, has been identified as a powerful risk factor for future cardiovascular morbidity and mortality. The risk of acute myocardial infarction, congestive heart failure, sudden death, and other cardiovascular events increases six- to e...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1991-01-01 00:00:00
abstract：:Microvascular pericytes contain predominantly endothelin A (ET(A))-like binding sites and also a smaller number of ETB binding sites. In this study we verified the expression of both receptors in these cells. We then examined the effect of insulin, a potent mediator of vasodilatation, on the expression of these recept...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Acute hemodynamic effects of 5 and 10 mg i.v. UD-CG 115 BS (pimobendan) were studied by right and left heart catheterization in idiopathic dilated cardiomyopathy (NYHA classes II and III; 5 mg = group I, n = 6; 10 mg = group II, n = 6). Effects on left ventricular function were evaluated by left ventricular angiograms...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1989-01-01 00:00:00
abstract：:The purpose of the two double-blind studies summarized in this article was to compare the antianginal and anti-ischemic effects of nicorandil with those of two different nitrate preparations. A total of 129 patients with stable New York Heart Association functional class II or III coronary heart disease were enrolled ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：1992-01-01 00:00:00
abstract：:Compound LY249933 and its component diastereomers, (RR) and (SR), were studied for their vascular and cardiac effects in vitro and in vivo. In guinea pig cardiac ventricular membranes, LY249933, (RR), and (SR) potently displaced bound [3H]nitrendipine (Kd values = 2-6 nM). In isolated guinea pig right ventricular stri...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:Calcium-antagonist drugs are therapeutic agents of first choice in patients with coronary artery disease. We have reviewed a number of clinical trials in which the safety and efficacy of calcium blockers have been tested and discuss the established clinical effects of these compounds, which range from relief of angina...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1992-01-01 00:00:00
abstract：:We wished to determine whether pharmacologic inhibition of the exaggerated sympathetic nerve activity in congestive heart failure (CHF) could restore the renal response to exogenous atrial natriuretic peptide (ANP) administration. Left ventricular (LV) myocardial infarction was induced in Sprague-Dawley rats (n = 16) ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199011000-00013
更新日期：1990-11-01 00:00:00
abstract：:The regulation of coronary hemodynamics is a complex process. One important factor that interferes with the regulation of coronary tone is the pathophysiological state of the vessels: stimuli that in normal vessels provoke no or only a slight vasoconstriction may cause a severe vasoconstriction in diseased vessels. Th...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1992-01-01 00:00:00
abstract：:In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York He...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-199424050-00007
更新日期：1994-11-01 00:00:00
abstract：:Measurements of cerebrospinal fluid (CSF) catecholamines (CA) were made in an attempt to estimate the activity of central CA neurons in essential hypertension (EHT). CSF norepinephrine (NE), epinephrine (EPI), and dopamine (DA) levels were measured in 12 normotensive (age 36 +/- 3 years; SBP = 116 +/- 4 and DBP = 79 +...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,评审
doi：
更新日期：1987-01-01 00:00:00
abstract：:From the membrane fraction of cultured human renal adenocarcinoma (ACHN) cells, two endothelin-2-converting enzymes (ECE-2A and ECE-2B) were solubilized with detergent Lubrol PX and separated by hydrophobic butyl fast-performance liquid chromatography. The pH range of the converting activity of ECE-2B for big endothel...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199322008-00018
更新日期：1993-01-01 00:00:00
abstract：:In the absence of formal clinical trials, the efficacy of thiazide diuretics in patients with renal impairment remains in doubt. Our study was therefore designed to evaluate the separate and combined effects of single and multiple doses of hydrochlorothiazide (HCTZ) and furosemide (FU) on the glomerular filtration rat...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199509000-00008
更新日期：1995-09-01 00:00:00
abstract：:The autonomic nervous system exerts broad control over the involuntary functions of the human body through complex equilibrium between sympathetic and parasympathetic tone. Imbalance in this equilibrium is associated with a multitude of cardiovascular outcomes, including mortality. The cardiovascular static state of t...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000559
更新日期：2018-03-01 00:00:00
abstract：:The sensitivity of smooth muscle from aortas of spontaneously hypertensive rats (SHR), renal hypertensive rats: two kidney-one clip and one kidney-one clip (2K-1C, 1K-1C) and DOCA salt hypertensive rats to the relaxant effect of nifedipine (NIF) was studied. A parallel leftward shift of the concentration-relaxation cu...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198609000-00005
更新日期：1986-09-01 00:00:00
abstract：:We investigated the effect of apstatin (an aminopeptidase P inhibitor) on bradykinin-induced inositol 1,4,5-triphosphate (IP3) formation and glucose uptake in isolated neonatal rat cardiomyocytes. Apstatin enhanced bradykinin-induced IP3 formation in a dose-dependent manner. We found that 1 microM Hoe 140 (a bradykini...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200105000-00001
更新日期：2001-05-01 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：:Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-198807000-00012
更新日期：1988-07-01 00:00:00
abstract：:Fibric acid-shaped drugs raise high-density lipoprotein (HDL) cholesterol by upregulating the HDL-related genes through activating peroxisome proliferater activated receptor (PPAR)-alpha. We investigated the effects of fibrates to induce expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181624b22
更新日期：2008-03-01 00:00:00
abstract：:Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is implicated in the pathogenesis of reperfusion injury, we examined the effect of SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction. ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199202000-00009
更新日期：1992-02-01 00:00:00
abstract：:This study was undertaken to determine and confer the cardioprotective effects of the adenosine A2 receptor (A2AR) and its impact on myocardial autophagy in the setting of reperfusion. We established a rat ischemia model by subjecting rats to 30 minutes of ischemia (I) and 120 minutes of reperfusion (R). The A2AR agon...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000239
更新日期：2015-07-01 00:00:00
abstract：:Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel activity in VF using sodium channel blockers. In nonischemic isolated feline hearts, the following electrophysiologic parameters were measured before and after application ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200012000-00015
更新日期：2000-12-01 00:00:00
abstract：:Experiments were designed to examine mechanisms of relaxations to nitric oxide (NO) in venous smooth muscle. Rings of canine femoral veins without endothelium were suspended for measurement of isometric force in organ chambers. Concentration-response curves to NO and 8-Br-cyclic guanosine monophosphate (cGMP) were obt...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199909000-00014
更新日期：1999-09-01 00:00:00
abstract：:Several mechanisms have been suggested for the absence of reflex tachycardia in response to the hypotensive effect of the selective alpha 1-adrenoceptor antagonist indoramin, including, in animals, membrane-stabilising activity, prolongation of repolarisation time, and reduction in baroreflex sensitivity. The present ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-198803000-00004
更新日期：1988-03-01 00:00:00
abstract：:The serotonin (5-HT2A) antagonistic activities and the protective effect on laurate-induced peripheral vascular lesions of AT-1015, a novel 5-HT2 receptor antagonist, were investigated. In platelet aggregation, AT-1015 selectively inhibited in vitro 5-HT2A receptor-mediated aggregation, and the activity was almost equ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200004000-00002
更新日期：2000-04-01 00:00:00
abstract：:We isolated two candidates for endogenous digitalis-like factors from human urine based on the inhibition of [3H]ouabain binding to intact human erythrocytes. The more-polar ouabain-displacing compound-1 (ODC-1) closely resembled ouabain in biological, physicochemical, and chromatographic properties. Moreover, anti-ou...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199322002-00019
更新日期：1993-01-01 00:00:00
abstract：:Formation of mature active neuropeptides such as substance P (SP) from their glycine extended precursors entails alpha-amidation of peptide precursors by the sequential enzymatic action of peptidylglycine alpha-monooxygenase (PAM) and peptidylamidoglycolate lyase (PGL). We reported that these two enzymes that can prod...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200006000-00007
更新日期：2000-06-01 00:00:00
