Abstract：
:Trans-diclofurime has been shown to be a very potent class II calcium antagonist (see preceding report), and we have examined its molecular interactions with the different receptor sites at the Ca2+ channel. Trans-diclofurime did not affect [3H]nitrendipine binding to rat cortical membranes at 37 degrees C and showed weak inhibitory effects at 25 degrees C, whereas at 0 degrees C 80% of the binding was inhibited noncompetitively (IC50, 13 nM); cis-diclofurime was 22-fold less potent. Trans-diclofurime, like diltiazem, blocked the inhibitory effects of verapamil on [3H]nitrendipine binding. Trans-diclofurime is a potent displacer of [3H]diltiazem binding (IC50, 15 nM; IC50 for diltiazem, 55 nM); the diclofurime isomers showed high stereoselectivity, with high Hill coefficients (0.85-1.0). In contrast, the stereoselectivity of the isomers was lower as inhibitors of [3H]verapamil binding, as were the Hill coefficients (0.55-0.65). It is proposed that the functional potency of the diclofurime isomers as calcium antagonists can be explained on the basis of their relative affinities for the diltiazem site and that this site is coupled to the dihydropyridine site in a positive heterotropic allosteric manner. A model for the interaction of group II calcium antagonists with the Ca2+ channel is proposed.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Mir AK,Spedding Mdoi
10.1097/00005344-198704000-00012subject
Has Abstractpub_date
1987-04-01 00:00:00pages
469-77issue
4eissn
0160-2446issn
1533-4023journal_volume
9pub_type
杂志文章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：:Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation, metastasis, and embryonic development. We previously demonstrated a nonchemotactic role for one such chemokine pair, stromal cell-derived factor-1α and its G-protein coupled receptor, CXCR4. Stromal cell-derive...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181f713fe
更新日期：2010-11-01 00:00:00
abstract：BACKGROUND:There is increasing evidence that endogenous sex hormones regulate vascular reactivity, and testosterone may contribute to the worse prognosis for renal disease in men. Male Zucker diabetic rats exhibit improved renal hemodynamic responses after castration. It is, however, unclear whether endogenous testoste...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/01.fjc.0000246941.84607.11
更新日期：2006-11-01 00:00:00
abstract：:To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air)....
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199312000-00018
更新日期：1993-12-01 00:00:00
abstract：:To evaluate the role of the sympathetic nervous system in essential hypertension and the influence of clonidine, 28 male subjects with mild to moderate hypertension were either treated with low-dose clonidine (n = 14, mean age: 42.4 +/- 2.1 years) or were randomized to a nontreated control group (n = 14, mean age: 40....
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：1987-01-01 00:00:00
abstract：:The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 mic...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199802000-00014
更新日期：1998-02-01 00:00:00
abstract：:Torsades de pointes ventricular tachycardia (VT) has been reported in patients taking the nonsedating antihistamine, terfenadine. We performed electrophysiologic studies of 14 isolated guinea pig hearts using the Langendorff technique to assess whether terfenadine exerted actions that could be responsible for inducing...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199501000-00006
更新日期：1995-01-01 00:00:00
abstract：:The effects of acetaldehyde (ACA) were examined in isolated electrically driven papillary muscle preparations from normal and streptozotocin-treated diabetic rats. Muscles from diabetic rats developed greater tension than those from normal rats. In muscles from both groups, ACA caused concentration-dependent negative ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:The primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The rapid resetting of arterial baroreceptor afferents toward any sustained new level of blood pressure ensures that the reflex acts as an effective buffer of short-term bloo...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1995-01-01 00:00:00
abstract：:This study attempted to characterize Ca2+ channels involved in endothelin-1-induced contraction of rabbit basilar artery using whole-cell patch-clamp and measurement of intracellular free Ca2+ concentration. Endothelin-1 activates two types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) and a store...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200209000-00013
更新日期：2002-09-01 00:00:00
abstract：:Populations with a high sodium intake have a high prevalence of hypertension and a high mortality and morbidity due to cerebrovascular disease. Within populations, however, it is very difficult to demonstrate a significant correlation between sodium intake and blood pressure. Experimental evidence exists demonstrating...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198400061-00030
更新日期：1984-01-01 00:00:00
abstract：:The aim of this study was to determine whether a quantitative relation exists between changes in regional myocardial blood flow (RMBF) and those in electrophysiologic determinants recorded via left ventricular endocardial and epicardial bipolar electrograms after administration of disopyramide (DP) and a class III ant...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199908000-00014
更新日期：1999-08-01 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：: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：:Several mechanisms of action for Ca2+ antagonists are possible at the vascular muscle cell membrane and at subsequent steps. In rat caudal artery, nitrendipine hyperpolarizes the resting vascular muscle cell, an action different from that of verapamil. Hyperpolarization might be expected to explain the relaxant action...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:We investigated the vasoactive actions of the wound-healing agent tetrachlorodecaoxygen (TCDO). TCDO (20 microM) had no direct effect on tone in isolated calf pulmonary arteries precontracted with potassium with or without 1 microM reduced hemoglobin under O2 or N2 atmosphere. However, TCDO, in a reduced hemoglobin-de...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199404000-00022
更新日期：1994-04-01 00:00:00
abstract：:Three-month-old spontaneously hypertensive rats were treated for 1, 2, or 3 months with daily intraperitoneal injections of naftidrofuryl (30 mg/kg). Systolic arterial pressure was measured. Tail arteries were removed and perfused at a constant flow rate of 2 ml/min. A concentration-response curve for serotonin was pr...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:The vasoconstrictor effects of endothelin-1 (ET-1) and norepinephrine (NE) were compared in the exteriorized rat mesentery in situ. ET-1 was 1,000 times more potent than NE in constricting both arterioles and venules. Vasoconstrictions induced by ET-1 lasted much longer than those caused by the catecholamine. At nonre...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198900135-00056
更新日期：1989-01-01 00:00:00
abstract：:We investigated the hemodynamic and inotropic effects of the new class III antiarrhythmic drug melperone. In eight pentobarbital-anesthetized dogs, the effects of intravenous melperone 0.5, 2.5, and 12.5 mg/kg-1 were tested. During atrial pacing we measured cardiac output (CO), mean aortic blood pressure (MAP), right ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198207000-00017
更新日期：1982-07-01 00:00:00
abstract：:To evaluate the safety and pharmacologic activity of ITF 296 in humans, three groups of healthy male normotensive subjects were studied. The first two groups (six subjects each) received, in ascending order, three dose levels of ITF 296 by 30-min intravenous infusion (group I, 0.1, 0.5, 1.0 microgram/kg/min; group II,...
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：1995-01-01 00:00:00
abstract：:We studied 12 patients receiving either chronic oral (p.o.) maintenance bretylium and/or acute intravenous (i.v.) bretylium to evaluate drug efficacy and pharmacokinetics. All patients were survivors of ventricular tachycardia or fibrillation. A new assay for bretylium was applied, and it proved sensitive and reliable...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198105000-00008
更新日期：1981-05-01 00:00:00
abstract：:Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199212000-00017
更新日期：1992-12-01 00:00:00
abstract：:The effects of a newly synthesized antiarrhythmic agent, TYB-3823 on the transmembrane action potential were examined in isolated papillary muscles of guinea pig. TYB-3823 (3 x 10(-6)-3 x 10(-5)M) caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of action potential duration (AP...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Acute occlusion of a coronary artery can result in myocardial infarction-a leading cause of premature death. Prompt restoration of blood flow to the myocardium can prevent excessive death of cardiomyocytes and improve clinical outcome. Although the major mechanism of cell death after reperfusion is necrosis, it is now...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000694
更新日期：2019-09-01 00:00:00
abstract：:The hypothesis that local release of prostanoids may contribute to the pharmacologic effect of nitroglycerin (NTG) has long been debated. Results of prostanoid blockade by indomethacin on NTG-induced effects, to date, have been inconclusive. To quantitate the effects of intravenous indomethacin on NTG-induced myocardi...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199712000-00005
更新日期：1997-12-01 00:00:00
abstract：:Selection of the appropriate dose of a new drug for initiation of treatment and then for maintenance is a complicated task. It requires the careful assessment and weighing of benefit vs. risk. A series of studies was carried out with lacidipine to determine the optimal initial dose in a general hypertensive population...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验,评审
doi：
更新日期：1991-01-01 00:00:00
abstract：:To assess dose-related effects of enalapril, we treated eight hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin converting-enzyme blocking drug. After a few days of placebo treatment, enalapril was given in single daily doses, starting with 1.25 mg and i...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198600081-00006
更新日期：1986-01-01 00:00:00
abstract：:Binge drinking of alcohol causes cardiac dysfunction in some people. The mechanism remains unclear. This study was designed to investigate high doses of alcohol-induced oxidative stress and apoptosis in cardiomyocytes and protective effects of antioxidants. Cardiomyocytes isolated from 1- to 2-day-old Sprague-Dawley r...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200412000-00012
更新日期：2004-12-01 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：:It has been proposed that cholinergic agonists inhibit the sinoatrial node discharge by shifting the activation range of the hyperpolarization-activated inward current If to more negative values or by increasing potassium conductance. In the former instance, cesium will potentiate the cholinergic inhibition by blockin...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200102000-00005
更新日期：2001-02-01 00:00:00
