Abstract:
:Clopidogrel is metabolically activated by cytochrome P450 (CYP) isoenzymes. We evaluated whether St. John's wort (SJW), a CYP2C19 and CYP3A4 inducer, enhances the pharmacodynamic response of clopidogrel. Volunteers (n = 45) were screened for clopidogrel hyporesponsiveness after a 300-mg load. After a 7-day washout, hyporesponders (n = 10) received 14 days of SJW (300 mg 3 times a day) followed by a second 300-mg clopidogrel. Platelet aggregation was measured at 0, 2, 4, and 6 hours postloading; hepatic CYP3A4 activity was simultaneously determined at 0 and 4 hours by the erythromycin breath test. A prospective, randomized, double-blind pilot study was conducted in postcoronary stent patients (n = 85) on clopidogrel 75 mg/d screened for clopidogrel hyporesponsiveness. Hyporesponders (n = 20) were randomized to SJW (n = 10) or placebo (n = 10); platelet aggregation was measured before and after 14 days of therapy. In volunteers, SJW decreased platelet aggregation (59% ± 14% vs. 40% ± 15% at 2 hours, P = 0.02; 56% ± 10% vs. 44% ± 13% at 4 hours, P < 0.03; and 55% ± 14% vs. 37% ± 14% at 6 hours, P = 0.01) and increased CYP3A4 activity (2.1% ± 0.4% CO2 exhaled per hour before vs. 2.9% ± 0.6% CO2 exhaled per hour after SJW, P = 0.002). In patients, SJW decreased platelet reactivity (226 ± 39 vs. 185 ± 49 P2Y12 reactivity units, P = 0.0002) and increased platelet inhibition (23% ± 11% vs. 41% ± 16%, P = 0.002). SJW may be a future therapeutic option to increase CYP metabolic activity and antiplatelet effect of clopidogrel in hyporesponders.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Lau WC,Welch TD,Shields T,Rubenfire M,Tantry US,Gurbel PAdoi
10.1097/FJC.0b013e3181ffe8d0subject
Has Abstractpub_date
2011-01-01 00:00:00pages
86-93issue
1eissn
0160-2446issn
1533-4023journal_volume
57pub_type
杂志文章,随机对照试验abstract::In an 8-week, double-blind, randomized, active-controlled, multicenter study with three parallel treatment groups, we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as monotherapy in patients with moderate to severe hypertension. Hypertensive out-p...
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:10.1097/00005344-199507000-00018
更新日期:1995-07-01 00:00:00
abstract::The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4-methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255 specifically bound to porcine aortic smooth muscle membranes expressing only ET(A) receptors with a K...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200104000-00014
更新日期:2001-04-01 00:00:00
abstract::This article presents selected aspects of the presynaptic modulation of noradrenaline release from the heart. Several presynaptic effector systems that mediate either inhibition or facilitation of noradrenaline release are discussed. In particular, the potencies of muscarinic agonists and antimuscarinic drugs in musca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198500075-00002
更新日期:1985-01-01 00:00:00
abstract::Halothane opposes cardiotoxicity of neutral-sugar digitalis compounds in intact animals, presumably by depressing a sympathetic component of arrhythmogenesis. However, halothane also produces a dose-related reduction in arrhythmogenicity of ouabain in isolated canine Purkinje fibers, suggesting that the anesthetic may...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199406000-00006
更新日期:1994-06-01 00:00:00
abstract::The serotonin-2 receptor antagonist ketanserin has been suggested to diminish arteriosclerotic development by its effect on platelet function and on vascular smooth muscle cells. We investigated the ability of ketanserin in reducing immune-mediated arteriosclerosis using the BN-WAG and WAG-BN rat aortic transplantatio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199603000-00001
更新日期:1996-03-01 00:00:00
abstract::Establishing the overall efficacy or safety of a drug requires a unified methodological approach and analysis of all clinical trials that are intended to be summarized. As an example, this article presents the aggregated dose-response relationship and a subgroup analysis (by age) over all studies of the antihypertensi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,meta分析
doi:10.1097/00005344-199219001-00025
更新日期:1992-01-01 00:00:00
abstract:UNLABELLED:Oxidative stress is an important risk factor in the pathogenesis of atherosclerosis. Angiotensin-converting enzyme (ACE) inhibitors attenuate atherosclerosis and oxidative stress in animal models. Omapatrilat, a VasoPeptidase-inhibitor, selectively inhibits both Neutral-Endo-Peptidase (NEP) and ACE. OBJECTI...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200401000-00021
更新日期:2004-01-01 00:00:00
abstract::The electrophysiologic effects of acutely and chronically administered amiodarone on canine Purkinje fibers were assessed using microelectrode techniques to record intracellular action potentials. Chronically treated dogs received amiodarone for 3 weeks (serum levels, 0.91 +/- 0.09 microgram/ml or 1.42 X 10(-6) M). Ac...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 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::The mechanism of lithium action, an effective treatment for bipolar disease, is still unknown. The present study examined the role of nitric oxide (NO) and prostaglandin systems in lithium modulation of acetylcholine in mesenteric vascular bed of rats by cannulating superior mesenteric artery. Acetylcholine (ACh) or s...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318153f262
更新日期:2007-12-01 00:00:00
abstract::Interest in the cardiovascular protective effects of calcium channel antagonists has increased in the past decade. We investigated prevention of vascular wall remodeling by the long-acting calcium channel antagonist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with high-salt-induced (4% NaCl) hypertension....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199406000-00016
更新日期:1994-06-01 00:00:00
abstract::Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198706107-00030
更新日期:1987-01-01 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::A contribution by active vasodilation to the hypotensive effect of medroxalol was investigated in anesthetized dogs and reserpinized pithed rats. In anesthetized dogs, intravenous doses of medroxalol, which decreased blood pressure and heart rate, also produced a dose-related vasodilation in the isolated perfused grac...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198301000-00022
更新日期:1983-01-01 00:00:00
abstract::We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200312001-00013
更新日期:2003-12-01 00:00:00
abstract::The present study was undertaken to investigate the interaction between endothelin-1 (ET-1) and norepinephrine (NE) on contractile regulation in dog ventricular myocardium. ET-1 alone did not elicit any inotropic response in isolated dog ventricular trabeculae (37 degrees C, 0.5 Hz). In the presence of NE at a high co...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200000006-00004
更新日期:2000-01-01 00:00:00
abstract::Atrial Fibrillation (AF) is accompanied by an increased risk for thromboembolic events in most affected patients. Current guidelines therefore recommend antithrombotic therapy with vitamin K antagonist (VKA) or non VKA oral anticoagulant (NOAC) in the majority of AF patients. Current AF treatment guidelines recommend ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000297
更新日期:2015-12-01 00:00:00
abstract::We wished to determine if the previously observed cardioprotective effects of monophosphoryl lipid A (MLA, 65 micrograms/kg intravenously, i.v.), an endotoxin derivative, were time related and mediated by an enhancement of antioxidant defense mechanisms, i.e., myocardial catalase and superoxide dismutase (SOD) activit...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199310000-00021
更新日期:1993-10-01 00:00:00
abstract::The purpose of this study was to examine whether tetrahydrobiopterin (BH4), one of the cofactors of nitric oxide (NO) synthase, attenuates endothelial cell death induced by 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), which is known to produce both superoxide and NO. Endothelial cell death was assessed by the rel...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199902000-00018
更新日期:1999-02-01 00:00:00
abstract::Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with hydrochlorothiazie (HCTZ) in 145 patients with mild to moderate hypertension. After 4 weeks of single-blind placebo runin, patients were randomly allocated to receive amlodipine (2.5-10 mg once daily, n = 97) or HCTZ (25-100 mg once da...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198812007-00022
更新日期:1988-01-01 00:00:00
abstract::We produced transgenic mice overexpressing Na+/ H+ exchanger as a model of salt-sensitive hypertension and reported that dietary salt loading elevates blood pressure in these transgenic mice. We speculate that this blood pressure elevation may be attributed to the elevation of intraarterial smooth muscle Ca2+ concentr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00024
更新日期:2000-03-01 00:00:00
abstract::Angiotensin-converting enzyme (ACE) is a widely distributed dipeptidyl carboxydipeptidase. Using computer analysis of the binding of radiolabeled ACE inhibitors, we have mapped the distribution of ACE in normal animals and in models of disease, and have studied the tissue effects of ACE inhibitors. In the myocardium, ...
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::The renin-angiotensin system affects blood pressure and regional blood flow through endocrine, paracrine, and autocrine influences. The circulating endocrine renin-angiotensin system (RAS) is activated for acute cardiovascular homeostasis. The recent demonstration of a local renin-angiotensin system in the blood vesse...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::[125I]Endothelin-1 (ET-1) was administered intravenously into rats, and binding sites in various tissues were examined by electron-microscopic radioautography. Labeling was observed predominantly on the glomerular fenestrated endothelial cells of kidney, alveolar capillary endothelial cells of lung, fat-storing cells ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00130
更新日期:1991-01-01 00:00:00
abstract::Acute ischemic left ventricular failure was induced in dogs by coronary embolization with plastic microspheres, resulting in reduced cardiac output (CO), increased left ventricular end-diastolic pressure (LVEDP), pulmonary capillary pressure (PCP), and total peripheral resistance (TPR). Intravenous (i.v.) administrati...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198907000-00018
更新日期:1989-07-01 00:00:00
abstract::Our previous study found that angiotensin-converting enzyme (ACE) inhibitors and amlodipine induce NO release from coronary microvessels through a kinin-dependent mechanism. The goal of this study was to determine whether amlodipine could potentiate NO formation during ACE inhibition. Coronary microvessels were isolat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200002000-00004
更新日期:2000-02-01 00:00:00
abstract::Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Carvedilol (20 mg/kg, bid) or vehicle was given to rats surviving a myocardial infarction (MI) 24 h (n = 409). In rats with large MI, carvedilol partially preserved left ventricular (LV) function and intrinsic myocardial contractility and reactivity to beta-adrenergic stimulation. Carvedilol led to scar thickening, in...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200201000-00009
更新日期:2002-01-01 00:00:00
abstract::Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or "signalosomes" are importan...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000206
更新日期:2015-03-01 00:00:00
abstract::The cardiac and renal hemodynamic effects of SE2395, a beta-blocking agent, were examined after intravenous administration (50 micrograms/kg) in normotensive conscious dogs. Beta-blocking action of SE2395 was evidenced by a reduction in heart rate and cardiac output without change in the mean arterial pressure. An inc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198511000-00029
更新日期:1985-11-01 00:00:00