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 and presence of palmitate during demand-induced ischemia of the rodent isolated hearts. Palmitate concentration-dependently increased FOX, decreased GOX, and increased MVO2. CVT-4325 inhibited FOX and increased GOX in the presence (but not the absence) of 1.2 mM palmitate, with EC50 values of 0.9 and 5.8 microM, respectively. The potency for CVT-4325 to inhibit FOX was 10-fold greater (0.9 versus 9.7 microM) in the presence of 1.2 mM compared with 0.4 mM palmitate. The increase in MVO2 caused by 1.2 mM palmitate was significantly reduced by 3 to 10 microM CVT-4325 in guinea pig hearts. In the presence of 1.2 mM palmitate, an increase in pacing rate of the guinea pig heart from 3.5 to 6.5 Hz caused a significant 50% increase in MVO2, a decrease in cardiac efficiency, and an increase in lactate concentration in the cardiac effluent from 0.04 +/- 0.01 to 0.10 +/- 0.02 mM (P < 0.01). CVT-4325 (3 microM) attenuated the increase (P < 0.05) in MVO2 while maintaining cardiac contractility, and decreased the lactate production to 0.05 +/- 0.01 mM (P < 0.01). Thus, the FOX inhibitor CVT-4325 decreased MVO2 and increased myocardial efficiency during demand-(pacing)-induced ischemia in the presence of palmitate in the rodent isolated hearts.

journal_name

J Cardiovasc Pharmacol

authors

Wu L,Belardinelli L,Fraser H

doi

10.1097/FJC.0b013e318166803b

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

372-9

issue

4

eissn

0160-2446

issn

1533-4023

pii

00005344-200804000-00005

journal_volume

51

pub_type

杂志文章
  • Effect of antioxidants on atherosclerotic plaque formation in balloon-denuded and irradiated hypercholesterolemic rabbits.

    abstract::The oxidative modification of low-density lipoprotein (LDL) hypothesis implies that antioxidants should be effective in suppressing atherosclerosis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and irradiated hypercholesterolemic rabbits....

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000179436.03502.26

    authors: Leborgne L,Pakala R,Dilcher C,Hellinga D,Seabron R,Tio FO,Waksman R

    更新日期:2005-10-01 00:00:00

  • The serotonin transporter is present and functional in peripheral arterial smooth muscle.

    abstract::We tested the hypothesis that the 5-HT transporter (5-HTT) is present and functional in peripheral arterial smooth muscle. In aorta and mesenteric resistance arteries, real time RT-PCR and western analyses indicated the presence of 5-HTT mRNA and a 74 kDa 5-HTT protein. Immunohistochemistry localized the transporter t...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200406000-00006

    authors: Ni W,Thompson JM,Northcott CA,Lookingland K,Watts SW

    更新日期:2004-06-01 00:00:00

  • Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498.

    abstract::The effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, HOE 498, and its prodrug on reperfusion arrhythmias after 15 min of coronary ligation were investigated in the isolated rat heart. Drug concentrations were equipotent in their effect on angiotensin I pressor response. Furthermore, ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: van Gilst WH,de Graeff PA,Wesseling H,de Langen CD

    更新日期:1986-07-01 00:00:00

  • Experimental myocardial infarction in adjuvant arthritis rats.

    abstract::We studied the influence of various inflammatory reactions on the survival rate and occurrence of arrhythmias in the acute phase of experimental myocardial infarction in conscious male Sprague--Dawley CFY rats. Chronic disseminated inflammatory disease was induced by subplantar injection of Freund complete adjuvant, w...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198205000-00004

    authors: Koltai M,Leprán I,Nemecz G,Szekeres L

    更新日期:1982-05-01 00:00:00

  • Depressor effect of intrathecal neuropeptide Y (NPY) Is mediated by Y2 subtype of NPY receptors.

    abstract::The effect of intrathecal administration of neuropeptide Y (NPY), NPY COOH-terminal fragments as well as an NPY Y1 receptor ligand on arterial blood pressure (ABP) of anesthetized rat was studied. NPY and all NPY COOH-terminal fragments tested (NPY11-36, NPY14-36 and NPY18-36), believed to act through Y2 receptors pro...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199305000-00005

    authors: Chen X,Westfall TC

    更新日期:1993-05-01 00:00:00

  • Electrophysiologic, antiarrhythmic, and cardioprotective effects of N-[3,5 dichlorophenyl] 4-[4-hydroxy-2-methoxy-phenyl] piperazine carboxamidine dihydrochloride (RS-87337).

    abstract::N-[3,5-Dichlorophenyl] 4-[4-hydroxy-2-methoxy-phenyl] piperazine carboxamidine dihydrochloride (RS-87337) is a chemically novel antiarrhythmic agent with an electrophysiologic profile characteristic of both class III and class Ia compounds as defined by Vaughan-Williams and Campbell. In isolated superfused guinea pig ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198908000-00002

    authors: Dumez D,Patmore L,Ferrandon P,Allely M,Armstrong JM

    更新日期:1989-08-01 00:00:00

  • Efficacy and safety of spirapril in mild-to-moderate hypertension.

    abstract::Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor. It is a prodrug with a resorption of about 50%. The active metabolite spiraprilat reaches maximal plasma concentration within 2-3 h after oral administration. Spirapril can be administered once daily because of its long duration of action caused by an e...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-199908001-00004

    authors: Hayduk K,Kraul H

    更新日期:1999-08-01 00:00:00

  • Effects of p38 MAPK Inhibitor on angiotensin II-dependent hypertension, organ damage, and superoxide anion production.

    abstract::Angiotensin II (Ang II) activates p38 mitogen-activated protein kinase (p38 MAPK) and increases reactive oxygen species (ROS), but the nature of the relationship in vivo is not fully understood. We assess the effect of SB239063AN, a highly selective, orally active, p38 MAPK inhibitor, on Ang II-dependent hypertension,...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e318046f34a

    authors: Bao W,Behm DJ,Nerurkar SS,Ao Z,Bentley R,Mirabile RC,Johns DG,Woods TN,Doe CP,Coatney RW,Ohlstein JF,Douglas SA,Willette RN,Yue TL

    更新日期:2007-06-01 00:00:00

  • Effect of rapamycin on rat aortic ring vasomotion.

    abstract::Rapamycin (RAPA) is an antifungal antibiotic with interesting new immunosuppressive properties. We evaluated RAPA's effects in vitro on basal and stimulated tension of isolated intact or denuded rat aortic rings. Rings were prepared in an organ chamber and contracted with 40 mM KCl (reference 100%). Some rings were tr...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199424050-00017

    authors: Corbin F,Blaise GA,Parent M,Chen H,Daloze PM

    更新日期:1994-11-01 00:00:00

  • Plasma erythrocyte relationship of catecholamines in human blood.

    abstract::The equilibrating process of catecholamines (CAs) between plasma and red blood cells (RBC) was studied by measuring their erythrocyte/plasma concentration gradient (E/P ratio); ratio of E/P > 1 for a given amine was considered the consequence of its accumulation in or on RBC. We studied in vitro human blood obtained f...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199404000-00002

    authors: Azoui R,Vignon D,Safar M,Cuche JL

    更新日期:1994-04-01 00:00:00

  • Antioxidant effects of angiotensin-converting enzyme (ACE) inhibitors: free radical and oxidant scavenging are sulfhydryl dependent, but lipid peroxidation is inhibited by both sulfhydryl- and nonsulfhydryl-containing ACE inhibitors.

    abstract::With an assay that generates free radicals (FR) through photooxidation of dianisidine sensitized by riboflavin, 4 x 10(-5) M captopril, epicaptopril (SQ 14,534, captopril's stereoisomer), zofenopril, and fentiapril [all sulfhydryl (-SH)-containing angiotensin-converting enzyme (ACE) inhibitors] were shown effective sc...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199203000-00005

    authors: Chopra M,Beswick H,Clapperton M,Dargie HJ,Smith WE,McMurray J

    更新日期:1992-03-01 00:00:00

  • Central and systemic effects of a vasopressin V1 antagonist on MAP recovery after haemorrhage in rats.

    abstract::The present study examined the effects of central and peripheral administration of a vascular (V1) vasopressin (AVP) receptor antagonist on blood pressure, heart rate, and AVP levels in conscious rats. Rats subjected to rapid arterial haemorrhage were administered the AVP V1 antagonist [d(CH2)5Tyr(Me)AVP] either 5 min...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198810000-00005

    authors: Johnson JV,Bennett GW,Hatton R

    更新日期:1988-10-01 00:00:00

  • Thapsigargin inhibits the response to acetylcholine and substance P but does not interfere with the responses to endothelium-independent agents.

    abstract::We investigated the influence of the Ca(2+)-ATPase inhibitor thapsigargin (TG) on the vasorelaxant response to different endothelium-dependent and endothelium-independent relaxing agents in an isolated thoracic aorta preparation of the rabbit, precontracted by norepinephrine (NE). Pretreatment with 100 microM L-argini...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199607000-00013

    authors: Amerini S,Filippi S,Parenti A,Ziche M,Ledda F

    更新日期:1996-07-01 00:00:00

  • No evidence for a direct vasodilatory effect of celiprolol on human vasculature in vivo or in vitro.

    abstract::Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arteri...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198711000-00015

    authors: Hughes A,Martin G,Goldberg P,Thom S,Sever P

    更新日期:1987-11-01 00:00:00

  • Left ventricular hypertrophy: a pressure-independent cardiovascular risk factor.

    abstract::Left ventricular hypertrophy (LVH), an increase in the muscle mass of the left ventricle, has been identified as a powerful risk factor for future cardiovascular morbidity and mortality. The risk of acute myocardial infarction, congestive heart failure, sudden death, and other cardiovascular events increases sixfold t...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Messerli FH,Ketelhut R

    更新日期:1993-01-01 00:00:00

  • Experimental pulmonary embolus in the rat: a new in vivo model to test thrombolytic drugs.

    abstract::Currently, the effects of the thrombolytic drugs are tested in vivo in dog or rabbit models that require a relatively large amount of the drug. The goal of the present study was to describe a new model that would allow one to test the in vivo thrombolytic effect of drugs with a limited amount of compound. For this pur...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198811000-00004

    authors: Clozel JP,Holvoet P,Tschopp T

    更新日期:1988-01-01 00:00:00

  • Effect of endothelin-1 and sarafotoxin S6c on blood flow in a rat tumor.

    abstract::The modification of tumor blood flow resulting from administration of endothelin-1 (ET-1) and sarafotoxin S6c (SX6c) was examined in female CBH rats. Blood flow in subcutaneous HSN tumors and normal tissues was measured by tissue uptake of 125I-labeled iodoantipyrine ([125I])IAP). A 75% increase in tumor blood flow wa...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Bell KM,Prise VE,Chaplin DJ,Tozer GM

    更新日期:1995-01-01 00:00:00

  • Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs.

    abstract::This study was designed to examine whether physiologically tolerable insulin, which maintains lower blood glucose, can protect the myocardium against ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary blood fl...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000249873.73197.c3

    authors: Zhang HX,Zang YM,Huo JH,Liang SJ,Zhang HF,Wang YM,Fan Q,Guo WY,Wang HC,Gao F

    更新日期:2006-12-01 00:00:00

  • Effect of morning and bedtime dosing with cilnidipine on blood pressure, heart rate, and sympathetic nervous activity in essential hypertensive patients.

    abstract::Cilnidipine has a blocking action against N-type calcium channels as well as L-type calcium channels. We studied the effect of morning and bedtime dosing on circadian variation of blood pressure (BP), heart rate (HR), and activity of the autonomic nervous system, using an open randomized crossover study in 13 essentia...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-200401000-00011

    authors: Kitahara Y,Saito F,Akao M,Fujita H,Takahashi A,Taguchi H,Hino T,Otsuka Y,Kushiro T,Kanmatsuse K

    更新日期:2004-01-01 00:00:00

  • Diminished responses to nifedipine imply severe end-organ damage in spontaneously hypertensive rats.

    abstract::This study was designed to investigate the effect of end-organ damage (EOD), the initial blood pressure levels, and baroreflex sensitivity (BRS) on the blood pressure-lowering effect of nifedipine in spontaneously hypertensive rats (SHRs). Nifedipine was intravenously administered at a dose of 1 mg/kg. BP was continuo...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000189077.71730.b8

    authors: Lu LH,Xie HH,Cai GJ,Shen FM,Su DF

    更新日期:2005-12-01 00:00:00

  • Verapamil-induced vasodilation is enhanced in essential hypertension.

    abstract::The dependency of arteriolar tone on calcium influx was studied in 11 patients with essential hypertension (EHT) and compared to 11 age-matched normotensive (NT) subjects by measuring the forearm blood flow (FAF) response to intraarterial infusion of the calcium channel blocker verapamil (Verap) and the nonspecific va...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Hulthén UL,Bolli P,Amann FW,Kiowski W,Bühler FR

    更新日期:1982-01-01 00:00:00

  • Decreased density of alpha 2-adrenoceptors in medulla oblongata of spontaneously hypertensive rats.

    abstract::To study the role of medullary alpha-adrenoceptors in hypertension, we compared specific binding of [3H]prazosin and [3H]clonidine in different brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), and normotensive Wistar-Kyoto rats (WKY). As compared with age-matched WKY, Bmax values for s...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198903000-00012

    authors: Yamada S,Ashizawa N,Nakayama K,Tomita T,Hayashi E

    更新日期:1989-03-01 00:00:00

  • Endothelin-1 limits vascular smooth muscle beta-adrenergic receptor sensitivity by a PKC-dependent pathway.

    abstract::Endothelin-1 reduces the chronotropic and inotropic effects of the beta-adrenoceptor agonist isoproterenol in rabbit isolated atria. Vascular interactions between endothelin-1 and isoproterenol have not been reported. Rings of the rabbit aorta without endothelium were mounted on myographs to measure isometric tension....

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200310000-00012

    authors: Gilbert P,Thorin E

    更新日期:2003-10-01 00:00:00

  • Estrogen receptor-mediated vascular responsiveness to nebivolol: a novel endothelium-related mechanism of therapeutic vasorelaxation.

    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

    authors: Garbán HJ,Buga GM,Ignarro LJ

    更新日期:2004-05-01 00:00:00

  • Analysis of responses to a selective phosphodiesterase III inhibitor, SK&F 94120, on isolated myocardium, including human ventricular myocardium from "end-stage" failure patients.

    abstract::The actions of SK&F 94120, a selective phosphodiesterase (PDE III) inhibitor, have been characterised on human ventricular myocardium obtained from heart failure patients. Some actions have been compared directly with those of the drug on guinea pig and cat ventricular myocardium. SK&F 94120 caused positive inotropic ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198706000-00013

    authors: Gristwood RW,English TA,Wallwork J,Sampford KA,Owen DA

    更新日期:1987-06-01 00:00:00

  • The inhibition of long-chain fatty acyl-CoA synthetase by enoximone in rat heart mitochondria.

    abstract::The mechanism by which enoximone, a reported phosphodiesterase inhibitor, inhibits the oxidation of long-chain fatty acids was studied in isolated rat heart mitochondria using a series of 14C-labeled substrates. Enoximone decreased palmitate oxidation in a time- and concentration-dependent manner. Fifty percent inhibi...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199206000-00009

    authors: Abdel-aleem S,Youssef J,Badr M,Morgan P,Frangakis C

    更新日期:1992-06-01 00:00:00

  • Coronary vascular hemodynamic and permeability changes during reperfusion after no-flow ischemia in isolated, diltiazem-treated rabbit hearts.

    abstract::Effects of diltiazem on coronary vascular functional integrity were assessed in isolated rabbit hearts during reperfusion after 30 min of global, no-flow ischemia. External detection of radiolabeled albumin, [125I]bovine serum albumin ([125I]BSA), and compartmental-model analysis were used to estimate the mean transit...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198505000-00003

    authors: Tilton RG,Williamson EK,Cole PA,Larson KB,Kilo C,Williamson JR

    更新日期:1985-05-01 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

  • Terfenadine increases the QT interval in isolated guinea pig heart.

    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

    authors: Pinney SP,Koller BS,Franz MR,Woosley RL

    更新日期:1995-01-01 00:00:00

  • Fenofibrate and pioglitazone do not ameliorate the altered vascular reactivity in aorta of isoproterenol-treated rats.

    abstract::Chronic stimulation of beta-adrenoceptors with isoproterenol induces alteration of vascular reactivity and increases local pro-inflammatory cytokines. We investigated whether fenofibrate and pioglitazone, PPAR-alpha and -gamma agonists, respectively, improve the changes in vascular reactivity induced by isoproterenol....

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e31818a8927

    authors: Fukuda LE,Davel AP,Verissimo-Filho S,Lopes LR,Cachofeiro V,Lahera V,Rossoni LV

    更新日期:2008-11-01 00:00:00