Abstract:
:Nonsedating H1-receptor antagonists appear to have wide and variable effects on the QT interval, mediated through modulation of cardiac K+ channels. By using the whole-cell patch-clamp technique, we examined the effects of terfenadine, loratadine, and descarboethoxyloratadine on a large family of K+ channels in ventricular myocytes and in Xenopus oocytes expressing the HERG delayed rectifier. The channels studied included the inward rectifier (I(Kl)) of rat and guinea pig, the transient outward K+ current (I(to)) of rat, the maintained K+ current (I(ped)) of rat, and the delayed rectifier K+ channels (I(Ks) and I(Kr)) of guinea pig myocytes. Loratadine and descarboethoxyloratadine, at therapeutic concentrations (30 to 100 nM), had no measurable effect on any one of the five types of K+ channels studied. At higher concentrations, 0.3 to 1.0 microM, only terfenadine had a significant suppressive effect on I(Kl) and delayed rectifier K+ channels, I(Kr) and I(Ks). At higher concentrations (1 to 2.5 microM), there were marked differences in the ability of the three drugs to suppress the five K+ channels. Generally, terfenadine was the most and loratadine, the least effective blocker of all K+ channels examined. The most susceptible K+ channels were the delayed rectifier channels (I(Ks) and I(Kr)) in guinea pig and I(ped) in rat myocytes. Comparative effects of loratadine and terfenadine examined on the I(Kr) channel (HERG) expressed in Xenopus oocytes suggest much higher affinity of this channel to terfenadine, such that 1 microM terfenadine completely suppressed the current, whereas loratadine had little or no effect. The preferential suppressive effect of terfenadine on the expressed HERG channel was consistent with data obtained on I(Kr) in isolated guinea pig ventricular myocytes. The strong suppressive effect of terfenadine, noted particularly on the I(Kr) and to a lesser extent on I(to), I(Kl), and I(Ks), may be the cause of the reported incidence of QT prolongation and arrhythmogenesis. The absence of significant effect of loratadine and descarboethoxyloratadine, especially on I(Kr), I(to), I(ped), and I(Kl), even at 100 x highest plasma concentrations achieved, may explain the absence of significant reports of QT prolongation and arrhythmogenesis by the latter drugs.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Ducic I,Ko CM,Shuba Y,Morad Mdoi
10.1097/00005344-199707000-00007subject
Has Abstractpub_date
1997-07-01 00:00:00pages
42-54issue
1eissn
0160-2446issn
1533-4023journal_volume
30pub_type
杂志文章abstract::To assess the cardiac functional reserve of elderly hypertensive patients with left ventricular hypertrophy (LVH) we studied cardiac function after isometric exercise and beta-adrenergic stimulation. Forty-five elderly hypertensive and 16 normotensive patients (NC group) were recruited for the study. The hypertensive ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199117002-00030
更新日期:1991-01-01 00:00:00
abstract::We studied the effect of 2-week treatment with estradiol 17beta on myocardial glutathione concentration in dogs and isolated perfused rat heart subjected to brief coronary ischemia and reperfusion. Estradiol protected against ischemia/reperfusion-induced myocardial systolic shortening and malonylaldehyde production an...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199809000-00017
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Telmisartan is an angiotensin II receptor blocker, which acts as a partial agonist of peroxisome proliferator activator receptor-γ (PPAR-γ). Because PPAR-γ initiates a variety of antiinflammatory responses, the effect on myocardial ischemia is to be elucidated. METHODS AND RESULTS:The left anterior descendi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3182592d7b
更新日期:2012-08-01 00:00:00
abstract::An acetylcholinesterase inhibitor (donepezil hydrochloride) has recently been used for the treatment of senile dementia of Alzheimer type. The effect of this acetylcholinesterase inhibitor on the autonomic nervous control of the heart was investigated in 17 patients with senile dementia of Alzheimer type. Donepezil ad...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::We evaluated the antiischemic effects of nifedipine in isolated working rat hearts from age-matched normotensive Wistar-Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR), and diabetic SHR. Diabetes was induced by streptozotocin. First, we constructed concentration-response curves for the negative i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::Guanfacine 3 mg was infused into six volunteers over 1 h on two occasions to investigate whether its sympatholytic effect is centrally or peripherally mediated. On one occasion, the central effects of guanfacine were blocked by prior administration of idazoxan 0.2 mg/kg i.v. (45 min preguanfacine); central alpha 2-blo...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198500076-00027
更新日期:1985-01-01 00:00:00
abstract::The possible relevance of intrinsic sympathomimetic activity (ISA) for beta-blocker-induced changes in plasma lipids was investigated by reviewing the literature and analyzing the results separately for nonselective beta-blockers, beta 1-selective beta-blockers, and those possessing ISA. It was confirmed that with the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198300051-00008
更新日期:1983-01-01 00:00:00
abstract::We investigated the endothelin (ET) receptors involved in the vasoconstrictor responses to ET-1 in rat pulmonary arteries and arterioles and the effect of endothelium removal, nitric oxide (NO) synthase inhibition, and hypoxia on ET-1-induced responses in the arteries. In isolated rat pulmonary artery rings (2-3 mm ID...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199405000-00022
更新日期:1994-05-01 00:00:00
abstract::Approximately 40-50% of the patients with end-stage cardiac failure (either ischemic or nonischemic) die suddenly and unexpectedly, most probably from ventricular fibrillation. It is unclear whether the complex ventricular arrhythmias observed in large numbers of these patients were related to the mode of death. Theor...
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::This randomized, double-blind, parallel-group study compared felodipine and hydrochlorothiazide (HCT) given in addition to a beta-blocker in 134 elderly hypertensive patients aged 56-79 years (mean of 66 +/- 5 years). In the felodipine-treated group (n = 57), supine blood pressure (BP) was reduced from 171 +/- 16/101 ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199015004-00030
更新日期:1990-01-01 00:00:00
abstract::In fetal human left ventricular endocardial endothelial cells (EECLs), both plasma membrane (PM) ET(A)R and ET(B)R were reported to mediate ET-1-induced increase of intracellular calcium [Ca](i); however, this effect was mediated by ET(A)R in right EECs (EECRs). In this study, we verified whether, as for the PM, nucle...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000242
更新日期:2015-07-01 00:00:00
abstract::We studied the influence of prostacyclin (PGI2) on the contractile performance of isolated mammalian ventricular muscle. PGI2 had no direct influence on myocardial contractility, as evidenced by experiments on single cardiac cells and papillary muscle. Moreover, PGI2 did not interfere with the inotropic action of isop...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198509000-00025
更新日期:1985-09-01 00:00:00
abstract::An attempt was made to study possible interaction between neuromodulation by adenosine and nicotine stimulatory effects. Dose-effect curves were made double blind in 7 nonsmoking, nonsnuffing healthy volunteers (25-49 years) before and during exposition to nicotine roughly corresponding to the nicotine of one cigarett...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199012000-00015
更新日期:1990-12-01 00:00:00
abstract::Nebivolol is a highly selective and lipophilic beta1-adrenergic receptor antagonist with vasodilating characteristics attributed mainly to endothelial generation of nitric oxide (NO). Coincidently, rapid vascular vasodilating effects of estradiol are also widely reported and membrane-initiated signaling by estrogen re...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200405000-00005
更新日期:2004-05-01 00:00:00
abstract::To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in diseased hearts, ANP levels in atrial and ventricular tissues and plasma were investigated in mice with congestive heart failure after viral myocarditis. The study was performed on day 14 after encephalomyocarditis viral inoculation, w...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::The aim of this study was to examine the electrophysiological effects of isoprenaline, phenylephrine, and noradrenaline on sheep Purkinje fibers in vitro, superfused either with a normal or with a modified physiological salt solution (PSS) designed to mimic some of the conditions occurring during mild myocardial ische...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198902000-00018
更新日期:1989-02-01 00:00:00
abstract::Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which is identified as an endogenous ligand for GH secretagogues receptor. Although both ghrelin and its specific receptor are expressed in blood vessels, the cardiovascular effects of ghrelin remain unknown. To clarify whether ghreli...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200206000-00001
更新日期:2002-06-01 00:00:00
abstract::Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), whic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198005000-00010
更新日期:1980-01-01 00:00:00
abstract::Endothelin-1 (ET-1) stimulated cAMP formation in Chinese hamster ovary cells stably expressing human wild-type ET(A) (CHO/hET(A) cells) and inhibited the formation in cells expressing human wild-type ETB (CHO/hETB cells), suggesting a selective coupling of hET(A) and hETB with G alpha s and G alpha i, respectively. To...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Data are presented that define the risks of elevated blood pressure, both systolic and diastolic, and support the recent recommendations of the Third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure in the United States that a consistently elevated pressure level above 140/90 mm ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-198507001-00020
更新日期:1985-01-01 00:00:00
abstract::Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced by endothelial cells of blood vessels. This peptide has quite a unique structure and pharmacological properties. ET-1 is produced in endothelial cells and may be secreted in a similar way to some paracrine hormones. The pressor response of ET-1 is large...
journal_title:Journal of cardiovascular pharmacology
pub_type: 历史文章,杂志文章,评审
doi:10.1097/00005344-198900135-00002
更新日期:1989-01-01 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::The efficacy and safety of carvedilol, a beta-blocker with vasodilatory properties, were compared with that of hydrochlorothiazide (HCTZ) both at a once-daily dose of 25-50 mg in a double-blind, randomized, parallel-group, multicenter study. Following a single-blind placebo phase of 3-6 weeks, 201 eligible patients (a...
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:1991-01-01 00:00:00
abstract::We compared the beta-adrenoceptor blocking actions of bupuranolol and propranolol using the response to isoprenaline of the strength of contraction of the canine blood-perfused ventricular muscle, of the rate and strength of contraction of the isolated guinea pig heart and of a guinea pig tracheal ring preparation. Th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-197903000-00004
更新日期:1979-03-01 00:00:00
abstract::Both acetylcholine (ACh) and cyclopiazonic acid (CPA) caused vasodilation of the mesenteric arterial bed in a concentration-dependent manner. When the mesenteric arterial bed was perfused with 0.1% Triton X-100 for 30 s, ACh- or CPA-induced vasodilation was almost abolished. ACh-induced vasodilation was significantly ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199604000-00022
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND:The sympathetic nervous system (SNS) of the whole body, including cardiac sympathetic nerves, is activated in patients with severe congestive systolic heart failure (CHF). Carvedilol can improve clinical status in such patients. This study aimed to determine how carvedilol acts on the SNS to improve CHF. ME...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/FJC.0b013e31823a94a2
更新日期:2012-02-01 00:00:00
abstract::MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was in...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198712000-00013
更新日期:1987-12-01 00:00:00
abstract::The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Schum. were examined in the rat isolated mesenteric arteries. 1H and 13C nuclear magnetic resonance spectra showed that cardamonin is present in trans-form, and single-crystal radiographic structure revealed that alpinetin is present in S configur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200105000-00011
更新日期:2001-05-01 00:00:00
abstract:INTRODUCTION:Newly emerging evidence showed that glucocorticoids could potentiate natriuretic peptides' action by increasing the density of natriuretic peptide receptor A, leading to a potent diuresis and a renal function improvement in patients with acute decompensated heart failure (ADHF). Therefore, glucocorticoid t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FJC.0000000000000048
更新日期:2014-04-01 00:00:00
abstract::We investigated the effects of an angiotensin-converting enzyme inhibitor (temocapril) and an angiotensin II type 1 receptor blocker (olmesartan) on changes in myocardial sympathetic nervous activity, fatty acid metabolism and myocardial blood flow using 131I-meta-iodobenzylguanidine, 125I-beta-methyl-iodophenyl penta...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00