Abstract:
:We have previously shown that amiloride suppresses the induction of sustained ventricular tachycardia both in dogs late following myocardial infarction and in patients. In those studies the only electrophysiologic correlate of amiloride's antiarrhythmic activity observed was prolongation of ventricular effective refractory period at the zone bordering the infarct. The purpose of this study was to assess the pharmacologic effects of amiloride associated with antiarrhythmic efficacy. However, amiloride has multiple pharmacologic effects, including inhibition of the slow inward calcium current (ICa), inhibition of the sodium-calcium and sodium-hydronium ion exchangers, acidification of intracellular pH resulting in partial inhibition of the inwardly rectifying potassium current (IK1), and increase in serum potassium and magnesium. The approach used in this study was to use selective pharmacologic probes to produce the known components of amiloride's pharmacologic effects. The selective agents consisted of verapamil (partial blockade of ICa), 3',4'-dichlorobenzamil (partial inhibition of the Na-Ca exchanger), 5-(N-ethyl-N-isopropyl) amiloride (partial inhibition of the Na-H exchanger), the combination of these congeners, KCl infusions to increase serum potassium, MgSO4 infusions to increase serum magnesium, the combination of KCl and MgSO4 infusions, barium (partial block of IK1), ryanodine (partial blockade of sarcoplasmic reticulum calcium release), and placebo. In this study only barium produced antiarrhythmic and electrophysiologic effects similar to those of amiloride. However, amiloride prolongs border zone refractoriness selectively, whereas barium prolongs refractoriness diffusely throughout the myocardium. Blockade of ICa by verapamil, increases in serum magnesium and potassium alone or in combination, and partial blockade of sarcoplasmic reticulum by ryanodine were not antiarrhythmic in this model. Monotherapies that produced partial blockade of the Na-Ca and Na-H exchangers separately did not produce antiarrhythmic activity. However, the combination of these amiloride congeners reproduced the antiarrhythmic activity of amiloride but did not prolong border zone refractoriness. From these studies we conclude that the antiarrhythmic activity of amiloride relates to (a) selective blockade of IK1 in the border zone and/or (b) combined inhibition of sodium-calcium and sodium-hydronium ion exchangers.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Duff HJ,Brown CE,Cragoe EJ,Rahmberg Mdoi
10.1097/00005344-199106000-00004subject
Has Abstractpub_date
1991-06-01 00:00:00pages
879-88issue
6eissn
0160-2446issn
1533-4023journal_volume
17pub_type
杂志文章abstract::The "Oxford" system for continuous monitoring of the ambulatory blood pressure was used to assess the changes in blood pressure following therapy with the calcium ion antagonists verapamil and nifedipine in two separate groups of patients. In the first group 16 patients were studied on both no therapy and following a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::The sympathetic drive to the cardiovascular system depends on the integrity of neurons in the medulla oblongata. The adrenergic neurons of the C1-area of the cortical ventrolateral medulla are tonically active and provide the background excitation of the spinal preganglionic neurons, which relay to the postganglionic ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198500073-00019
更新日期:1985-01-01 00:00:00
abstract::Apoptosis, a genetically controlled programmed cell death, has been found to play a role in ischemic reperfusion injury in several animal species including rats and rabbits. To examine whether this also is true for other animals, a surgically relevant model was established using an isolated in situ swine heart. Hearts...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200011000-00009
更新日期:2000-11-01 00:00:00
abstract::Activation of adrenoceptors of the alpha 2-subtype can cause an inhibitory or an excitatory response, depending on the cellular system affected. At the plasma membrane, where the extracellular signal is transduced via the alpha 2-adrenoceptor into an intracellular signal, only one transduction process has clearly been...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198500076-00018
更新日期:1985-01-01 00:00:00
abstract::Dietary omega-3 polyunsaturated fatty acids (PUFAs) are readily incorporated into heart and skeletal muscle membranes where, in the heart, animal studies show they reduce O2 consumption. To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans, the effects of fish oil (FO) supplementation on O2 consumpt...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181911913
更新日期:2008-12-01 00:00:00
abstract::Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. We aimed to investigate the roles of inflam...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318186a84d
更新日期:2008-09-01 00:00:00
abstract::By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly con...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/01.fjc.0000211762.06271.ce
更新日期:2006-05-01 00:00:00
abstract::Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-200301000-00016
更新日期:2003-01-01 00:00:00
abstract::Nitric oxide (NO) is a potent inhibitor of platelet aggregation. However, the benefits of NO-based therapies can be confounded by concomitant hypotension. Monophosphoryl lipid A (MLA) is a nontoxic derivative of endotoxin that purportedly increases nitric oxide synthase (NOS) activity and, presumably, NO production, y...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00004
更新日期:2000-03-01 00:00:00
abstract::Clopidogrel (CLO) is a clinical antiplatelet agent, about which there are major concerns because its antiplatelet efficiency decreases with insufficient metabolic activation, leading to "clopidogrel resistance." We aimed to determine the antiplatelet effects of W1, a novel molecule composed of 2-O-clopidogrel and aspi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000449
更新日期:2017-02-01 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::Several 3,5-pyridinedicarboxylic acid [4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-] esters, which are analogs to felodipine, were synthesized and tested for peroral activity and vascular selectivity. Structure-activity relationships demonstrate that felodipine has biological properties (selectivity and oral activ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198710001-00011
更新日期:1987-01-01 00:00:00
abstract::The acute and chronic arterial effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril were studied in hypertensive patients. Hemodynamic and biological parameters were measured 3 h after the first dose of 5 mg of ramipril, and then again after 4 weeks of treatment, 3 and 24 h after drug administration. ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::Vascular smooth muscle cell (VSMC) proliferation is pivotal in the progression of hypertension, atherosclerosis, and restenosis. Resveratrol is a grape polyphenol that is implicated as an important contributor to red wine's vascular protective effects. Its antimitogenic action on VSMC is attributed to an array of plei...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318059ae80
更新日期:2007-07-01 00:00:00
abstract::Disorders of the cardiac conduction system occur frequently and may cause life-threatening arrhythmias requiring medication or electronic pacemaker implantation. Repair or regeneration of conduction system components is currently not possible due to limited knowledge of the molecular regulation of pacemaker myocardium...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181e775d3
更新日期:2010-07-01 00:00:00
abstract::The sensitivity of smooth muscle from aortas of spontaneously hypertensive rats (SHR), renal hypertensive rats: two kidney-one clip and one kidney-one clip (2K-1C, 1K-1C) and DOCA salt hypertensive rats to the relaxant effect of nifedipine (NIF) was studied. A parallel leftward shift of the concentration-relaxation cu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198609000-00005
更新日期:1986-09-01 00:00:00
abstract::The elderly are reported to be less sensitive to the beta-blocking effects of propranolol. However, age-related changes in the stereoselective pharmacokinetics or protein binding of propranolol enantiomers could have confounded the results of previous studies because only 1-propranolol contributes significantly to the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199011000-00003
更新日期:1990-11-01 00:00:00
abstract::Myocardial alpha 1-adrenoceptor number has been reported to increase during ischaemia in myocytes consequent to an increase in acyl carnitine levels. We investigated whether this phenomenon occurs in vivo and whether the novel antiischaemic agent ranolazine will protect against it. Thirty-minute occlusion of the left ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199306000-00004
更新日期:1993-06-01 00:00:00
abstract::To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone-producing adenoma (APA), we have investigated ET-1 receptors by radioligand binding assay (RBA) in human normal adrenal (NA), APA, idiopathic hyperaldosteronism...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00059
更新日期:1998-01-01 00:00:00
abstract::We assessed the renal effects of moderate treadmill exercise in the spontaneously hypertensive rats (SHR) remnant kidney model of chronic renal failure (CRF). The effects of chronic administration of a specific endothelin (ET) subtype A (ETA) receptor antagonist, FR139317 (32 mg/kg/day i.p.) and an angiotensin-convert...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00139
更新日期:1998-01-01 00:00:00
abstract::Both population (mass) strategies and targeted strategies for the management of high blood pressure are necessary. However, it has yet to be proven that reducing blood pressure by lifestyle changes in the population will confer the same cardiovascular benefit that results from lowering blood pressure by drugs. It is i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199627003-00008
更新日期:1996-01-01 00:00:00
abstract::Calcium sensitizers increase myocardial contractile function without affecting Ca2+ homeostasis, which might be beneficial in the treatment of patients with heart failure. However, it remains uncertain whether Ca sensitizers induce quantitatively similar inotropic responses in control and failing hearts. To compare th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200101000-00003
更新日期:2001-01-01 00:00:00
abstract::The effects of streptozotocin (STZ)-induced diabetes (DM) and insulin on cardiac performance were investigated during reperfusion after low-flow ischemia in rats. Hearts were isolated 4 weeks after intravenous injection of STZ (65 mg/kg) or vehicle and retrogradely perfused in the presence (throughout the perfusion pe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200210000-00001
更新日期:2002-10-01 00:00:00
abstract::Using the radioactive microsphere technique, we studied the acute systemic and regional hemodynamic effects of felodipine (10, 30, and 100 nmol/kg, i.v.) in conscious renal hypertensive rabbits. A dose-dependent decrease in arterial blood pressure was observed after felodipine administration, accompanied by tachycardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198407000-00025
更新日期:1984-07-01 00:00:00
abstract::The effects of divalent cations on human platelet vasopressin receptor binding characteristics and effects of receptor occupancy on endogenous protein phosphorylation were investigated. Binding of vasopressin to its receptor is modulated by both the nature and the concentration of ions. Whatever the cation present, gu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198707000-00004
更新日期:1987-07-01 00:00:00
abstract::Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relax...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199204002-00030
更新日期:1992-01-01 00:00:00
abstract::This paper presents results on the function of the adrenal medulla, especially the influence of substance P (SP) on the cholinergic-adrenergic interaction. Interconnections between the function of SP and its role in the development and maintenance of hypertension as well as its role in stress and adaptation are invest...
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::Twenty-four-hour urinary sodium excretion and plasma renin activity were monitored in 36 patients receiving bendrofluazide as sole antihypertensive therapy. There was no increase in urinary sodium output compared with pretreatment values during a 2-year period, and there is therefore no evidence that an increase in sa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198400061-00039
更新日期:1984-01-01 00:00:00
abstract::Dihydropyridine calcium antagonists play an important role in the treatment of arterial hypertension. In many centers, they are used as first-line treatment. Since impaired renal function can be a complication of long-standing blood pressure elevation, the usefulness of dihydropyridine calcium antagonists in hypertens...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 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