Abstract:
:The new anti-anginal drug ranolazine causes a slight (<10 milliseconds) prolongation of the QT interval, raising the concern that its use may be associated with an increased incidence of torsades de pointes ventricular tachyarrhythmias. The goal of this study was to show that ranolazine inhibits the late component of INa and attenuates prolongation of action potential duration when late INa is increased, both in the absence and presence of IK-blocking drugs. Currents and action potentials of guinea pig isolated ventricular myocytes were measured by whole-cell patch clamp. Sea anemone toxin (ATX)-II was used to increase late INa and mimic the effect of an SCN5A gene mutation. ATX-II (3-5 nmol/L) increased late INa by 5-fold; ranolazine attenuated this increase of late INa by up to 61 +/- 8%. ATX-II (10-20 nmol/L) increased action potential duration (APD) by > 1 seconds, and caused early afterdepolarizations; both actions were attenuated by ranolazine (0.1-30 micromol/L). Ranolazine (10 micromol/L) reduced by 89% the 13.6-fold increase in variability of APD caused by 10 nmol/L ATX-II. The effects of ATX-II (3 nmol/L) in combinations with either the IKr blocker E-4031 or the IKs blocker chromanol 293B to increase APD were attenuated 76 +/- 5% and 71 +/- 4%, respectively, by 10 micromol/L ranolazine. The results demonstrate that ranolazine reduces late INa and has an anti-arrhythmic effect when late INa is increased.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Song Y,Shryock JC,Wu L,Belardinelli Ldoi
10.1097/00005344-200408000-00008subject
Has Abstractpub_date
2004-08-01 00:00:00pages
192-9issue
2eissn
0160-2446issn
1533-4023pii
00005344-200408000-00008journal_volume
44pub_type
杂志文章abstract::The effects of noradrenaline (NA) on the perfusion pressure of mesenteric vascular bed preparations from stroke-prone spontaneously hypertensive rats (SHRSP) or weight-matched normotensive Wistar-Kyoto (WKY) rats in the presence of chloroethylclonidine (CEC, alpha 1B-adrenoceptor antagonist) or WB4101 (WB, alpha 1A-ad...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199507000-00013
更新日期:1995-07-01 00:00:00
abstract::It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential in...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-200301000-00006
更新日期:2003-01-01 00:00:00
abstract::To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg),...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00088
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVE:Genetic loci predict <5% of variation in low-density lipoprotein cholesterol (LDL-C) response to statins. Cholestanol and desmosterol are plasma markers of cholesterol absorption and synthesis, respectively. Because statins lower LDL-C by inhibiting cholesterol synthesis, we studied the relationship between c...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/FJC.0b013e3181f09bcb
更新日期:2010-10-01 00:00:00
abstract::We investigated the role of endothelin-A (ETA) and endothelin-B (ETB) receptors in ischemia/reperfusion-induced cardiac dysfunction and norepinephrine overflow using isolated rat hearts. According to the Langendorff technique, isolated hearts were subjected to 40 minutes of global ischemia followed by 30 minutes of re...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166297.02819.f2
更新日期:2004-11-01 00:00:00
abstract::Nicorandil, ATP sensitive potassium channel opener, is shown to reduce coronary events for patients with stable angina. The present study was designed to examine the protective potential of nicorandil for patients undergoing off-pump coronary artery bypass grafting. Twenty-four patients undergoing off-pump coronary ar...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.fjc.0000141476.52125.5b
更新日期:2004-10-01 00:00:00
abstract::Endothelin-1 (ET-1) is synthesized and secreted by cardiomyocytes and induces cardiac hypertrophy. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a lipid-activated nuclear receptor that negatively regulates the vascular inflammatory gene response by interacting with transcription factors, such as nuc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166303.33313.01
更新日期:2004-11-01 00:00:00
abstract::Antecubital venous plasma neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamines were analyzed in six healthy volunteers performing a graded bicycle exercise without medication and after acute administration of clonidine, phentolamine, and nifedipine. During the control exercise, plasma noradrenaline (NA), a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198811000-00014
更新日期:1988-01-01 00:00:00
abstract::Endothelin-1 (ET-1) influences vascular function by modulating intracellular free Ca2+ concentration ([Ca2+]i) in smooth muscle. This study investigated the effects of ET-1 on [Ca2+]i and contractile responses in resistance vessels of young prehypertensive (5 week) and adult hypertensive (17 week) spontaneously hypert...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant for smooth muscle cells and fibroblasts in culture, is believed to play an important role in the formation of proliferative lesions of arterio-sclerosis. PDGF appears as three different dimeric isoforms: AA, AB, and BB. These were recently fou...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 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::alpha-Adrenoceptor agonists and antagonists are widely used perioperatively for internal mammary artery (IMA)-coronary artery bypass operations. To determine subtypes of alpha-adrenoceptors in the human IMA, we studied responses of isolated human IMA segments to alpha-adrenoceptor agonists, antagonists, and electrical...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 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::The target proteins for calcium, when it acts as a second messenger, are a group of intracellular, specific calcium-binding proteins that contain EF-hand structures. Calmodulin regulates a number of Ca2+-dependent processes and is present in all eukaryotic cells. Parvalbumin, the S-100 proteins, two vitamin D-dependen...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1986-01-01 00:00:00
abstract::The bronchopulmonary and pressor effects of endothelin-1 (ET-1), a newly described vasoconstrictor peptide produced by endothelial cells, were investigated in the guinea pig. Intravenous injection of ET-1 (1 nmol/kg) induced an increase in pulmonary inflation pressure (PIP) as well as an important and sustained increa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198900135-00036
更新日期:1989-01-01 00:00:00
abstract::In urban Australia, the risk of retiring with hypertension is greater than 40%, and the basic abnormality--a rise in blood pressure (BP) with age--is almost universal. A hypothesis linking this with salt, therefore, concerns everyone. The diet of early humans was unsalted, and the Na content of breast milk (6 mmol/kg)...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract::The comparative contributions of arachidonic acid (AA) metabolites and 5-hydroxytryptamine (5-HT) to the delay of reperfusion and rate of reocclusion after coronary thrombolysis with streptokinase were assessed in dogs using (a) single TXA2 synthase inhibition; (b) single 5-HT2-receptor blockade; (c) dual TXA2 synthas...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199301000-00009
更新日期:1993-01-01 00:00:00
abstract::We briefly review and compare the current knowledge of growth mechanisms for the mitogenic response of endothelial cells and smooth-muscle cells to injury. For the endothelium, this focuses on the evidence that growth control involves two components: an endogenous inhibition mechanism, which can be overcome either by ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199321001-00007
更新日期:1993-01-01 00:00:00
abstract::Few studies have addressed the possibility that brain natriuretic peptide (BNP) possesses a profile of bioactivity that is distinct from that of atrial natriuretic peptide (ANP). Accordingly, we assessed the biologic actions of BNP in the setting of maximal or near-maximal ANP-induced biologic activity. Background ANP...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199902000-00008
更新日期:1999-02-01 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::To evaluate the interaction between renal nerves, the atrial natriuretic peptide (ANP), and the renin-angiotensin system (RAS), electrical stimulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY), before and after pharmacologic treat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199611000-00009
更新日期:1996-11-01 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::At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-1 using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00159
更新日期:1998-01-01 00:00:00
abstract::Cardiac fibroblasts are the major non-myocyte cell constituent in the myocardium, and they are involved in heart remodeling. Angiotensin II type 1 receptor (AT1R) mediates the established actions of angiotensin II (Ang II), and changes in its expression have been reported in cardiac fibroblasts after myocardial infarc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318181fadd
更新日期:2008-08-01 00:00:00
abstract::The clinical pharmacokinetics and pharmacodynamics of enalapril and its de-esterified active metabolite, MK 422, were determined in eight patients with congestive cardiomyopathy and five patients with hypertension. After administration of single doses of 2.5, 5, and 10 mg enalapril in the congestive heart failure pati...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198507000-00023
更新日期:1985-07-01 00:00:00
abstract::Oxidative stress is believed to play a role in diabetes-induced vascular complications. In this study, we tested whether chronic treatment with a known hydroxyl radical scavenger, dimethylthiourea (DMTU), could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by an intravenous injectio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199612000-00002
更新日期:1996-12-01 00:00:00
abstract::To investigate the role of endothelin (ET) in severe hypertension, endothelial dysfunction hypercholesterolemic stroke-prone spontaneously hypertensive rats (SHRSP on a 5% cholesterol diet) were additionally fed with 1% NaCl and 0.023% nitro-L-arginine. Under these conditions, all untreated rats died within 30 days (m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00069
更新日期:1998-01-01 00:00:00
abstract::Calcium channel blockade appears to be at least as effective as beta-blockade in the treatment of anginal syndromes, but whether a similar protective effect is afforded against sudden death is unknown. In order to compare experimental antifibrillatory effects of calcium channel blockade (diltiazem), beta-adrenoceptor ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198409000-00007
更新日期:1984-09-01 00:00:00
abstract::Since minoxidil was previously shown to raise plasma renin activity (PRA) but not the plasma aldosterone concentration (PAC), the effect of minoxidil on the rate of aldosterone metabolic clearance was studied. After the addition of minoxidil to the antihypertensive regimen of 7 hypertensive patients, the aldosterone m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198000022-00018
更新日期:1980-01-01 00:00:00
abstract::: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000151
更新日期:2014-12-01 00:00:00