Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations.

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 injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure.

journal_name

J Cardiovasc Pharmacol

authors

Hosono M,Taira N

doi

10.1097/00005344-198712000-00013

subject

Has Abstract

pub_date

1987-12-01 00:00:00

pages

692-8

issue

6

eissn

0160-2446

issn

1533-4023

journal_volume

10

pub_type

杂志文章
  • Comparative study of the effects of lacidipine and enalapril on the left ventricular cardiomyocyte remodeling in spontaneously hypertensive rats.

    abstract::Antihypertensive medications are the most efficient drugs in achieving regression of myocardial hypertrophy in both clinical studies and animal models of hypertension. Nevertheless, there is a lack of clear and concise comparative study of their effects on the modulation of cardiomyocyte morphology and function. Here,...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000211728.23304.ad

    authors: Cagalinec M,Kyselovic J,Blaskova E,Bacharova L,Chorvat D Jr,Chorvatova A

    更新日期:2006-04-01 00:00:00

  • G protein-coupled receptor signaling in cardiac nuclear membranes.

    abstract::G protein-coupled receptors (GPCRs) play key physiological roles and represent a significant target for drug development. However, historically, drugs were developed with the understanding that GPCRs as a therapeutic target exist solely on cell surface membranes. More recently, GPCRs have been detected on intracellula...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/FJC.0000000000000196

    authors: Branco AF,Allen BG

    更新日期:2015-02-01 00:00:00

  • KATP channel activation mediates nicorandil-induced relaxation of nitrate-tolerant coronary arteries.

    abstract::We compared the tolerance-inducing effects of nitroglycerin (NTG) and nicorandil (NIC) in porcine isolated coronary arteries and assessed the role of KATP channels in the response to NIC in nitrate-tolerant and nontolerant preparations. In coronary arteries contracted with U46619 (1-3 x 10(-9) M), NTG, NIC, sodium nit...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199606000-00010

    authors: O'Rourke ST

    更新日期:1996-06-01 00:00:00

  • An explanation of bell-shaped, dose-positive inotropic effect curves for denopamine in canine right ventricular muscle.

    abstract::We investigated mechanisms by which denopamine produces bell-shaped, cumulative concentration-response curves for positive inotropic effect in canine right ventricular muscle. As in our previous study, the curves ascended at 10(-8) to 10(-6) M, reached a maximum at 3 X 10(-6) to 10(-5) M, and descended at higher conce...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198910000-00008

    authors: Yokoyama H,Ishii K,Yanagisawa T,Taira N

    更新日期:1989-10-01 00:00:00

  • R56865, a potent new antiarrhythmic agent, effective during ischemia and reperfusion in the rat heart.

    abstract::The antiarrhythmic effects of R56865 were characterized both in vivo and in vitro. Four groups (n = 12 per group) of anesthetized rats, subjected to 5- or 30-min coronary artery ligation and reperfusion, were studied: saline, dimethyl sulfoxide (DMSO) carrier, and R56865 (0.5 or 2 mg/kg) were administered as an intrav...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199009000-00018

    authors: Garner JA,Hearse DJ,Bernier M

    更新日期:1990-09-01 00:00:00

  • Treatment of transient myocardial ischemia in patients with stable angina: a comparative study of verapamil slow-release and nifedipine plus propranolol.

    abstract::We compared the effect of verapamil slow-release (VSR) and the combination of nifedipine plus propranolol on transient myocardial ischemia in a double-blind study comprising 20 patients with proven coronary artery disease and chronic stable angina. According to the results of 24-h Holter-monitoring recording, patients...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00005344-199204000-00024

    authors: Molinero E,Salcedo A,Sagastagoitia JD,Arzubiaga J,Iriarte MM,Gómez Pajuelo C,Fernández Vidal P

    更新日期:1992-04-01 00:00:00

  • Electrophysiological effects of a new antiarrhythmic agent, flecainide, on the intact canine heart.

    abstract::The cardiac electrophysiology of flecainide a new antiarrhythmic agent, was studied in open-chested dogs. At plasma concentrations of 0.4 to 0.7 microgram/ml, flecainide significantly prolonged atrioventricular (AV) conduction. At plasma concentrations greater than 6.5 micrograms/ml, flecainide caused delay throughout...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-197907000-00005

    authors: Hodess AB,Follansbee WP,Spear JF,Moore EN

    更新日期:1979-07-01 00:00:00

  • Simvastatin releases Ca2+ from a thapsigargin-sensitive pool and inhibits InsP3-dependent Ca2+ mobilization in vascular smooth muscle cells.

    abstract::Simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity inhibits migration and proliferation of vascular smooth muscle cells (SMC). To investigate whether these effects of SV are related to inhibition of cell calcium mobilization, cultured SMC obtained from rat aorta were l...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199603000-00011

    authors: Escobales N,Castro M,Altieri PI,Sanabria P

    更新日期:1996-03-01 00:00:00

  • Analysis of the electrophysiologic effects of short-term oxybutynin on guinea pig and rabbit ventricular cells.

    abstract::The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell-configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit pa...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200002000-00024

    authors: Jones SE,Kasamaki Y,Shuba LM,Ogura T,McCullough JR,McDonald TF

    更新日期:2000-02-01 00:00:00

  • Effects of the H2-receptor agonist impromidine in human myocardium from patients with heart failure due to mitral and aortic valve disease.

    abstract::We determined stimulation rates of cardiac adenylate cyclase activity by isoproterenol and impromidine in particulate sarcolemmal membrane preparations from human papillary muscles resected during open heart replacement of mitral and aortic valves. In addition, specific receptor binding studies with [3H]dihydroalpreno...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198307000-00017

    authors: Baumann G,Mercader D,Busch U,Felix SB,Loher U,Ludwig L,Sebening H,Heidecke CD,Hagl S,Sebening F,Blömer H

    更新日期:1983-07-01 00:00:00

  • Assessment of cardiac function by echocardiography in conscious and anesthetized mice: importance of the autonomic nervous system and disease state.

    abstract::In this study, the authors sought to evaluate the mechanisms responsible for echocardiographically determined differences in cardiac structure and function between conscious and anesthetized mice to determine whether such differences were more or less evident in diseased states. Cardiac parameters were determined by t...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200308000-00005

    authors: Tan TP,Gao XM,Krawczyszyn M,Feng X,Kiriazis H,Dart AM,Du XJ

    更新日期:2003-08-01 00:00:00

  • Intermittent clonidine regimen abolishes tolerance to its antihypertensive effect: a spectral study.

    abstract::The development of tolerance to the antihypertensive effect of clonidine and related imidazolines is clinically recognized. Here, we employed a restricted daytime (8:30 AM until 4:30 PM) clonidine regimen to establish a model of sustained hypotension in spontaneously hypertensive rats (SHRs). Blood pressure (BP), hear...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e3180318afb

    authors: El-Mas MM,Abdel-Rahman AA

    更新日期:2007-03-01 00:00:00

  • Dronedarone and Captisol-enabled amiodarone in an experimental cardiac arrest.

    abstract:OBJECTIVE:To compare the energy required for defibrillation and postshock outcomes after the administration of dronedarone, amiodarone, and placebo in a porcine model of cardiac arrest. METHODS:Forty-two pigs were randomized to amiodarone, dronedarone, or control treatments. After induction of ventricular fibrillation...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e3182868750

    authors: Glover BM,Hu X,Aves T,Ramadeen A,Zou L,Leong-Poi H,Fujii H,Dorian P

    更新日期:2013-05-01 00:00:00

  • Vasodilatory effect of ghrelin, an endogenous peptide from the stomach.

    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

    authors: Okumura H,Nagaya N,Enomoto M,Nakagawa E,Oya H,Kangawa K

    更新日期:2002-06-01 00:00:00

  • Design and synthesis of a potent and selective endothelin-converting enzyme inhibitor, CGS 35066.

    abstract::CGS 26303 has previously been shown to inhibit human endothelin converting enzyme-1 (ECE-1) with an IC50 of 410 nM and to be efficacious in several animal disease models. However, it is a more potent inhibitor of neutral endopeptidase 24.11 (NEP) with an IC50 of 1 nM. The aim of this study was to optimize CGS 26303 fo...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200036051-00014

    authors: Jeng AY,De Lombaert S,Beil ME,Bruseo CW,Savage P,Chou M,Trapani AJ

    更新日期:2000-11-01 00:00:00

  • Effects of two beta3-agonists, CGP 12177A and BRL 37344, on coronary flow and contractility in isolated guinea pig heart.

    abstract::The functional role of beta(3)-adrenergic receptors in the heart is still not clear. The actions of two widely used beta(3)-adrenoceptor agonists, such as BRL 37344 and CGP 12177, were studied in the isolated guinea pig heart, perfused at constant pressure according to the Langendorff technique. Heart contractility (d...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200305000-00006

    authors: Kozlovski VI,Chlopicki S,Gryglewski RJ

    更新日期:2003-05-01 00:00:00

  • Irisin Protects Heart Against Ischemia-Reperfusion Injury Through a SOD2-Dependent Mitochondria Mechanism.

    abstract::Irisin, a muscle-origin protein derived from the extracellular domain of the fibronectin domain-containing 5 protein (FNDC5), has been shown to modulate mitochondria welfare through paracrine action. Here, we test the hypothesis that irisin contributes to cardioprotection after myocardial infarction by preserving mito...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0000000000000608

    authors: Wang Z,Chen K,Han Y,Zhu H,Zhou X,Tan T,Zeng J,Zhang J,Liu Y,Li Y,Yao Y,Yi J,He D,Zhou J,Ma J,Zeng C

    更新日期:2018-12-01 00:00:00

  • Polarized secretion of endothelin-1 and big ET-1 in MDCK cells is inhibited by cell Na+ flux and disrupted by NH4Cl.

    abstract::We recently found that TGF-beta increases ET-1 secretion in MDCK, a renal tubular cell line. The secretion of ET-1, by a confluent monolayer of MDCK cells grown on a filter, to the basolateral side of the epithelium was two times greater than that to the apical side. However, TGF-beta-increased ET-1 and big ET-1 secre...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199100177-00065

    authors: Uchida S,Horie M,Yanagisawa M,Matsushita Y,Kurokawa K,Ogata E

    更新日期:1991-01-01 00:00:00

  • Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia.

    abstract::Formation of oxygen free radicals during heart transplantation seems to be related to the alterations occurring during ischemia and reperfusion and could explain the short preservation time of donor hearts. The aim of our study was (a) to analyze the protective effects of pyruvate during cold cardioplegia and ischemia...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199911000-00005

    authors: Dobsak P,Courderot-Masuyer C,Zeller M,Vergely C,Laubriet A,Assem M,Eicher JC,Teyssier JR,Wolf JE,Rochette L

    更新日期:1999-11-01 00:00:00

  • Relationship between the sympatholytic action of nebivolol and hypotension.

    abstract::Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/-...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Ward JE,Coles P,Cox H,Eisenhofer G,Angus JA

    更新日期:1992-07-01 00:00:00

  • Effects of adenosine and verapamil on anatomic no-reflow in a rabbit model of coronary artery occlusion and reperfusion.

    abstract::Adenosine and verapamil have successfully been used in the treatment of clinical no-reflow after direct angioplasty for acute myocardial infarction. However, their effects on anatomic perfusion defects in experimental myocardial ischemia/reperfusion are unknown. Thus the area of no-reflow (ANR), visualized after in-vi...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200404000-00014

    authors: Reffelmann T,Kloner RA

    更新日期:2004-04-01 00:00:00

  • Heritable abnormalities of the renin-angiotensin-aldosterone system in essential hypertension.

    abstract::A subset of essential hypertensives sensitive to salt and having normal or high renin levels are termed nonmodulators. These subjects fail to modulate their renal blood flow and aldosterone responsiveness when dietary sodium is changed. We have found that a positive family history of hypertension in a first degree rel...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Dluhy RG,Hopkins P,Hollenberg NK,Williams GH,Williams RR

    更新日期:1988-01-01 00:00:00

  • Protective effects of FK409, a novel nitric oxide donor, against postischemic myocardial dysfunction in guinea-pig hearts.

    abstract::Effects of FK409 were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Nitric oxide electrode, fluorometry, and 31P nuclear magnetic resonance imaging were used to monitor changes in cellular high-phosphorous energy and nitric oxide and Ca2+ content in the heart together wi...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200110000-00012

    authors: Cao Y,Hotta Y,Shioi K,Nagata Y,Kawai N,Ishikawa N

    更新日期:2001-10-01 00:00:00

  • The angiotensin receptor blocker, azilsartan medoxomil (TAK-491), suppresses vascular wall expression of plasminogen activator inhibitor type-I protein potentially facilitating the stabilization of atherosclerotic plaques.

    abstract::Increased expression of plasminogen activator inhibitor type-I (PAI-1) in vessel walls seems to accelerate atherosclerosis. Angiotensin II can increase the synthesis of PAI-1. Inhibition of this process may facilitate migration of vascular smooth muscle cells (VSMCs) stabilizing atherosclerotic plaques. To determine w...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e31821dcbea

    authors: French CJ,Zaman AK,Sobel BE

    更新日期:2011-08-01 00:00:00

  • Comparison of the frequency-dependent effects on the atrioventricular node of verapamil, amiodarone, digoxin, and diltiazem in isolated guinea pig hearts.

    abstract::To slow ventricular rate during supraventricular tachycardia, a drug must have a strong rate-dependent depressant effect on atrioventricular (AV) conduction. We investigated the frequency-dependent effects of verapamil, amiodarone, digoxin, and diltiazem on AV conduction time (AVCT) in isolated guinea pig heart perfus...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199502000-00020

    authors: Stark G,Schulze-Bauer C,Stark U,Kasper K,Decrinis M,Tritthart HA

    更新日期:1995-02-01 00:00:00

  • Pharmacologic approaches to the treatment of atherosclerotic arterial obstruction.

    abstract::Three consecutive periods in the natural history of atherosclerosis are amenable to medical treatment. Plaque development is the main target of prevention, which also aims at slowing the progression of already existing plaques. The control of several established risk factors (high blood cholesterol, high blood pressur...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-199500252-00009

    authors: Capron L

    更新日期:1995-01-01 00:00:00

  • Atrial fibrillation and the expanding role of catheter ablation: do antiarrhythmic drugs have a future?

    abstract::The main therapeutic strategies for treating atrial fibrillation include rate control, maintenance of sinus rhythm, and antiembolic treatment. Current antiarrhythmic drugs are effective in about 50% of patients and are often associated with adverse effects. Multiple trials suggest that rate control with proper anticoa...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/FJC.0b013e318175dd73

    authors: Naccarelli GV,Gonzalez MD

    更新日期:2008-09-01 00:00:00

  • Protective effects of carvedilol, a vasodilating beta-adrenoceptor blocker, against in vivo low density lipoprotein oxidation in essential hypertension.

    abstract::Low density lipoprotein (LDL) oxidation plays a crucial role in the development and progression of atherosclerosis and is enhanced in patients with essential hypertension. This finding has stimulated a search for antihypertensive drugs with high intrinsic antioxidant properties. We investigated the antihypertensive an...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00005344-199604000-00012

    authors: Maggi E,Marchesi E,Covini D,Negro C,Perani G,Bellomo G

    更新日期:1996-04-01 00:00:00

  • Modulation of alpha 1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: protection by ranolazine.

    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

    authors: Allely MC,Brown CM,Kenny BA,Kilpatrick AT,Martin A,Spedding M

    更新日期:1993-06-01 00:00:00

  • A novel partial fatty acid oxidation inhibitor decreases myocardial oxygen consumption and improves cardiac efficiency in demand-induced ischemic heart.

    abstract::The benefits of inhibition of fatty acid oxidation (FOX) and stimulation of glucose oxidation (GOX) in ischemia are controversial. The objective of this study was to evaluate the effect of the FOX inhibitor CVT-4325 on the rates of FOX, GOX, myocardial oxygen consumption (MVO2), and cardiac efficiency in the absence a...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e318166803b

    authors: Wu L,Belardinelli L,Fraser H

    更新日期:2008-04-01 00:00:00