Abstract:
:Pro-arrhythmia by noncardiac drugs has become an important safety concern in the pharmaceutical industry. The most common underlying mechanism for induction of arrhythmias by noncardiac drugs is off-target block of the native cardiac repolarizing current, I Kr. The pore-forming subunit of I Kr is encoded by the human ether-a-go-go related gene (hERG), and in vitro measurements of hERG activity has become a standard component of drug safety evaluations. hERG/I Kr channels are blocked by a wide array of different chemical series; therefore, patients could be exposed to multiple blockers. There are few published studies addressing whether multiple blockers will exert independent actions on hERG channels. Whole cell patch clamp was used to evaluate the potential for cooperative effects when 2 hERG blocking agents were applied simultaneously. Cisapride, quinidine, fluvoxamine, and BeKm-1 were selected as representative agents binding to: (1) hydrophobic residues in the inner vestibule (cisapride and quinidine, the most frequent sites of interaction), (2) an extracellular segment near the pore (BeKm-1) or, (3) an unknown site (fluvoxamine). No synergistic blocking actions were seen. In some cases block was slightly less than additive. On balance, the results are consistent with additive and independent actions with simultaneous application of 2 hERG blockers.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Margulis M,Sorota Sdoi
10.1097/FJC.0b013e31817532eesubject
Has Abstractpub_date
2008-06-01 00:00:00pages
549-52issue
6eissn
0160-2446issn
1533-4023journal_volume
51pub_type
杂志文章abstract::Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00054
更新日期:2000-11-01 00:00:00
abstract::Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose-indu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000844
更新日期:2020-08-01 00:00:00
abstract::Long-term effects of antihypertensive treatment on various electrocardiogram (ECG) voltages and the association between ECG findings at randomization and subsequent mortality were evaluated in the double-blind, placebo-controlled trial of elderly hypertensive patients, conducted by the European Working Party on High B...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199117002-00020
更新日期:1991-01-01 00:00:00
abstract::Recent in vitro experiments have shown that amrinone enhances the release of nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation. This in vivo study examined whether amrinone causes vasodilatation mediated by endothelium-derived NO, and whether this effect is attenuated in patients with endot...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-200008000-00008
更新日期:2000-08-01 00:00:00
abstract::This presentation has reviewed evidence from our laboratory that both structural and functional changes participate in the initiation and maintenance of hypertension in spontaneously hypertensive rats (SHR). Structural changes are present in the muscular arteries of the mesenteric and renal vasculature at 3- to 5-week...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198406004-00014
更新日期:1984-01-01 00:00:00
abstract::The effects of R 56,865, a compound with unusual calcium antagonistic properties, on altered left ventricular (LV) diastolic properties were studied during pacing-induced ischemia in dogs with coronary stenosis. Severe coronary artery stenosis was produced on both the left anterior descending (LAD) and circumflex (Cx)...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199104000-00015
更新日期:1991-04-01 00:00:00
abstract::Some recent studies complementing earlier reports on the pharmacology and pharmacokinetics of indoramin are briefly reviewed. Competitive blockade of peripheral postsynaptic alpha 1-adrenoceptors is confirmed as the primary mechanism for the antihypertensive activity of indoramin. Various reasons have been proposed to...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-198600082-00004
更新日期:1986-01-01 00:00:00
abstract::The electrophysiologic actions of the class III antiarrhythmic agents, GLG-V-13 and d,l-sotalol, were examined in superfused normal and ischemically injured epicardium. Both drugs produced concentration and reverse-use dependent prolongation of the action potential duration in normal myocardium without altering restin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3180ca959e
更新日期:2007-09-01 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::The evolutionary relationships among 17 protein and nucleic acid sequences from the sarafotoxin/endothelin/endothelin-like superfamily of peptides were studied. The endothelin/endothelin-like gene family has diverged from an ancestral gene that has experienced an exon duplication event followed by two complete gene du...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00148
更新日期:1991-01-01 00:00:00
abstract::Endothelin-1[1-31] is a recently discovered member of the endothelin family with vasoactive properties in several animal models and in man in vivo. It is generated from big endothelin-1 by human mast cell chymase and may be a novel intermediary peptide in the production of endothelin-1[1-21]. Given that both big endot...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166233.11336.67
更新日期:2004-11-01 00:00:00
abstract::Regeneration of the heart after a stroke would be the best biologic response to restore its function. However, although this phenomenon occurs in primitive organisms, the regenerative potential is lost in mammals. Thus, the search for an appropriate cardiac progenitor with the potential to differentiate into a functio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181d8bc6d
更新日期:2010-07-01 00:00:00
abstract::Electrophysiologic and antiarrhythmic effects of the new benzofurane derivative carocainide given intravenously have been studied in normal patients (Group I) and in patients with paroxysmal supraventricular tachycardias (Group II). In normal patients (n = 10), carocainide increased sinoatrial conduction time, PR, PA,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812000-00003
更新日期:1988-12-01 00:00:00
abstract::Hypertonic solutions of 0.3 M sodium chloride (NaCl) infused into the third ventricle (ICV) for 20 min in urethane-anesthetized rats consistently elevated mean aortic pressure by approximately 10 mm Hg. Heart rate and sympathetic nerve activity diminished slightly during the first few minutes but then accelerated to a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198409000-00017
更新日期:1984-09-01 00:00:00
abstract::Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. In this study we examined the influence of thyroid hormone status on immunoreactive endothelin (ir-ET...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00078
更新日期:1993-01-01 00:00:00
abstract::The haemodynamic effects of three different methods of nitrate administration [intravenous (i.v.) isosorbide dinitrate (ISDN) and buccal and transdermal nitroglycerin (NTG)] were evaluated in 36 patients with acute left ventricular failure due to a recent myocardial infarction. Similar reductions in pulmonary artery o...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198911000-00012
更新日期:1989-11-01 00:00:00
abstract::We compared platelet function results obtained with the VerifyNow P2Y12 (VN-P2Y12) point-of-care device and the light transmission aggregometry (5 and 20 microM adenosine diphosphate) method using an integrated database of eight clinical trials with a total of 591 subjects. The study was performed in healthy subjects,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181dd0ec2
更新日期:2010-07-01 00:00:00
abstract::The effects of various doses of creatine phosphate have been examined in a rat model of acute myocardial ischaemia. When given directly into the lumen of the left ventricle in pentobarbitone-anaesthetised male rats, creatine phosphate (50 and 100 mg/kg) markedly reduced the incidence of ventricular ectopic beats, and ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198201000-00009
更新日期:1982-01-01 00:00:00
abstract::Isolated Langendorff-perfused rat hearts set up to allow measurement of mechanical myocardial function (according to Bardenheuer and Schrader) were subjected to 60 min of global ischemia (gI). The hearts were perfused with a modified Krebs-Henseleit solution (KHS; control group) or KHS with desipramine (DMI group) 100...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198806121-00003
更新日期:1988-01-01 00:00:00
abstract::A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new angiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diure...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198700003-00021
更新日期:1987-01-01 00:00:00
abstract::Besides generating renal damage, hypertension plays an important role in the progression of diabetic nephropathy. The fructose-fed rat is a well-established model both of high blood pressure and renal impairment, which is similar to diabetic nephropathy. To clarify the relationship between hypertension, glucose metabo...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000138166.34482.56
更新日期:2004-09-01 00:00:00
abstract::Interspersed between cardiac myocytes, cardiac fibroblasts serve mainly as a structural support during ventricular wall thickening from embryogenesis until adulthood. Cardiac fibroblasts, however, may also serve as a source of mitogens, extracellular matrix proteins, cytokines, and growth factors that could affect the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e31821209ee
更新日期:2011-05-01 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::There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (T...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000199
更新日期:2015-04-01 00:00:00
abstract::Therapeutic response to angiotensin-converting enzyme (ACE) inhibitors was reported to be better related to tissular than to circulating levels of ACE inhibition, especially during chronic therapy. We studied the relations between plasma concentrations of angiotensin I (AI), plasma renin activity (PRA), angiotensin II...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199607000-00003
更新日期:1996-07-01 00:00:00
abstract::As cyclic 3',5'-guanosine monophosphate (cGMP) is still discussed as a possible mediator of the negative inotropic effects of cholinergic agents, the influence of acetylcholine (ACh) on force of contraction and cGMP tissue levels was studied in isolated, electrically driven guinea pig auricles in the presence of methy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198611000-00009
更新日期:1986-11-01 00:00:00
abstract::In addition to the hemodynamic components, the roles of various humoral factors have been emphasized in the progression of vascular and renal injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Sixteen nonhospitalized men, average age 41.3 years with essential hypertension (WHO I-II) were given nifedipine slow-release tablets of 20 mg twice daily for 48 weeks. Both supine and standing blood pressure values were significantly reduced, but heart rate was not significantly changed by the drug. A significant dec...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198501000-00003
更新日期:1985-01-01 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::To clarify further the relationships between parathyroid glands and the development of hypertension, we studied the effect of cross-transplantation of these glands from young hypertensive rats in normotensive recipients. The parathyroid glands were isolated in 5-week-old hypertensive rats of the Lyon (male and female)...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00