Abstract:
:Atherosclerosis is an inflammatory response to accumulation of cholesterol in the artery wall. Low-density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima during hypercholesterolemia, leading to activation of endothelial cells, macrophages, and T cells. We sought to define the role of oxidized LDL (oxLDL) in the poloxamer 407 (P-407)-induced mouse model of dose-dependent hyperlipidemia and atherosclerosis developed in our laboratory. The hyperlipidemic agent P-407 was evaluated for its ability to oxidize native LDL in vitro as determined by measuring the rate of formation of conjugated dienes, as well as malondialdehyde (MDA) production using the thiobarbituric acid reactive substances assay. Additionally, plasma obtained from C57BL/6 mice treated with P-407 for 100 days and maintained on either a normal diet or a diet supplemented with 0.5% w/w cholic acid was assayed for both MDA and lipid hydroperoxide content. Lastly, plasma from these same groups of mice was analyzed for the presence of immunoglobulin (Ig) G and IgM autoantibodies against oxLDL. Our results indicate that P-407 is unable to directly oxidize native LDL in vitro. However, plasma obtained from P-407-treated mice demonstrated a significant (P < 0.05) increase in the content of oxidized lipids, but showed a significant (P < 0.05) decrease in the concentration of lipid hydroperoxides when compared to controls. Both plasma IgG and IgM antibodies to MDA-modified LDL (MDA-LDL) were significantly (P < 0.05) elevated in P-407-treated mice, as was IgG1 anti-MDA-LDL, whereas the titer of IgG2a anti-MDA-LDL was significantly (P < 0.05) reduced. We suggest that P-407 causes oxidation of LDL in vivo by an indirect mechanism and we further conclude that P-407-induced hypercholesterolemia in C57BL/6 mice is associated with T cell-dependent (IgG) and T cell-independent (IgM) B-cell responses to MDA-LDL.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Johnston TP,Zhou Xdoi
10.1097/FJC.0b013e318032aa11subject
Has Abstractpub_date
2007-04-01 00:00:00pages
246-52issue
4eissn
0160-2446issn
1533-4023pii
00005344-200704000-00009journal_volume
49pub_type
杂志文章abstract::Carvedilol is a dual-acting drug designed to produce two complementary effects: beta-blockade and vasodilation. These effects are induced in the same dose range, a prerequisite for utilizing both properties in an appropriate manner. The vasodilation is mediated predominantly by specific alpha 1-adrenoceptor blockade. ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199219001-00003
更新日期:1992-01-01 00:00:00
abstract::Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in atherogenesis. Adipose tissue is an important source of endogenous TNFalpha production. The aim of this study was to evaluate the effect of atorvastatin on TNFalpha serum concentration and mRNA expressions of subcutaneous adipose in hyperch...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000167017.69468.61
更新日期:2005-08-01 00:00:00
abstract::Our recent studies have shown that the nonpeptide angiotensin II (Ang II) antagonist losartan interacts with thromboxane A2/prostaglandin H2 receptors and inhibits the thromboxane A2 (TxA2) analog U46619-induced vasoconstriction in canine coronary arteries. In this study, we further investigated whether losartan preve...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199808000-00005
更新日期:1998-08-01 00:00:00
abstract::We assessed the effect of phenytoin on serum lipids and lipoproteins in a group of 20 male volunteers. Nine of the subjects were healthy, and 11 had coronary heart disease. Their mean age was 44 +/- 7 years. Phenytoin was given at daily doses of 200-350 mg for a period of 4-9 months. Serum total cholesterol increased ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198101000-00019
更新日期:1981-01-01 00:00:00
abstract::Renal effects of a selective cyclooxygenase-2 (COX-2) inhibitor [MF-Tricyclic; 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone] were studied in control and volume-depleted conscious dogs. MF-Tricyclic was compared with the nonselective COX-1/COX-2 inhibitor indomethacin. Six instrumented male dogs ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199811000-00002
更新日期:1998-11-01 00:00:00
abstract:INTRODUCTION:We investigated the efficacy of carvedilol for preventing the recurrence of atrial fibrillation and reducing QT prolongation induced by bepridil. METHODS:We assigned 144 subjects with persistent atrial fibrillation. The subjects were divided into 3 groups: carvedilol plus bepridil, candesartan plus beprid...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3182790692
更新日期:2013-01-01 00:00:00
abstract::We studied the inotropic and possible antioxidant effects of levosimendan in human atrial strips, before and after induction of oxidative stress induced by H2O2. Levosimendan (10(-9) to 10(-6) M) increased contractions induced by electrical stimulation (ES) in human atrial strips. The maximal positive inotropic effect...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318123fbf9
更新日期:2007-10-01 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::Thirty-two hypertensive subjects with diastolic blood pressure greater than 95 mm Hg were treated with ramipril over a period of 3 months. To determine the effective decrease of blood pressure and for reliable and reproducible demonstration of regression of myocardial hypertrophy during ramipril treatment, we performe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198900133-00019
更新日期:1989-01-01 00:00:00
abstract::Development of tolerance to nicorandil (NCR), N-(2-hydroxyethyl)nicotinamide nitrate (ester), was compared with that to nitroglycerin (NTG) or isosorbide dinitrate (ISDN) in dogs. An intracoronary arterial (i.a.) injection of NCR (20 micrograms), ISDN (30 micrograms), or NTG (1 microgram) caused coronary vasodilation....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::During the healing phase of evolving myocardial infarction, inflammatory cells invade the affected region and produce metabolites that may influence electrophysiological parameters and the genesis of malignant arrhythmias. We have recently shown an increased synthetic capacity within an evolving infarct for thromboxan...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198511000-00009
更新日期:1985-11-01 00:00:00
abstract::To gain insight with regard to the mode of action of calcium antagonists on the vasculature, we examined the effects of nifedipine, isradipine, felodipine, verapamil, gallopamil, and amlodipine on vasoconstrictor-induced prostacyclin synthesis in vitro. Cultured rat aortic smooth muscle cells were seeded after two to ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199004000-00012
更新日期:1990-04-01 00:00:00
abstract::Endothelin (ET) may play an important role in the pathogenesis of vasoconstriction and acute renal failure after aortic cross-clamping (ACC). However, the relative contribution of the ET(A) and ET(B) receptors to the physiopathology of ischemic acute renal failure is poorly understood. This study was carried out to ev...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199908000-00004
更新日期:1999-08-01 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::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
更新日期:1994-11-01 00:00:00
abstract::Calcium-entry blockers were administered in an attempt to protect myocardium during cardiac arrest due to ventricular fibrillation in mechanically ventilated dogs. An intravenous injection of verapamil, nifedipine, or lidoflazine was administered prior to successively prolonged episodes of ventricular fibrillation, du...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 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::We conducted an intracardiac study of the electrophysiologic effects and kinetics of intravenous nicardipine (N) in 16 patients with or without impaired cardiac conduction, using a randomized, double-blind, crossover design versus placebo (P). N or P were infused intravenously over 5 min: the dose of N was 9.46 +/- 3....
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199001000-00021
更新日期:1990-01-01 00:00:00
abstract::We investigated the effect of different ACE inhibitors on tissue injury in isolated rat hearts subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Zofenoprilat (1-100 microM), but not enalaprilat or lisinopril, significantly reduced infarct size, as estimated on the basis of triphenyltetrazoliu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200402000-00020
更新日期:2004-02-01 00:00:00
abstract::The renin-angiotensin system (RAS) has been proposed to play a major role in causing the heart to hypertrophy during pressure overload. We examined whether blockade of this system by the angiotensin-converting enzyme (ACE) inhibitors enalapril (0.5 to 20 mg/kg p.o.) or ramipril (1.0 mg/kg p.o.) or the angiotensin rece...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199402000-00017
更新日期:1994-02-01 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:BACKGROUND:S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS:Twelve-week-old fema...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000220
更新日期:2015-05-01 00:00:00
abstract::We examined the effects of prolonged oral administration of oxprenolol (twice daily for 6 weeks) to male Sprague-Dawley rats. At two times (1 or 16-18 h) after the last oral dose, the rats were anaesthetised and subjected to acute coronary artery ligation, and the severity of the resulting arrhythmias was assessed. Is...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198405000-00001
更新日期:1984-05-01 00:00:00
abstract::Interventions that inhibit neutrophil infiltration into myocardial tissue after ischaemia and reperfusion are reported to reduce the size of the infarct. We examined whether administration of trimetazidine, which is reported to reduce myocardial infarct size, affects this process. [111In]Neutrophils and [125I]albumin ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199312000-00008
更新日期:1993-12-01 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::Calcium is a signaling element of general importance to cells. In muscle, its key function is the activation of troponin C, which is essential for the contraction of myofibrils in skeletal and heart muscles, and of myosin light chain kinase, which is essential for the contraction of smooth muscles. Calcium modulates t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00
abstract::Endocannabinoids, such as anandamide and 2-arachidonoylglycerol, are synthesized from membrane phospholipids in the heart and other cardiovascular tissues. They activate cannabinoid CB1 and CB2 receptors, transient receptor potential V1 (TRPV1), peroxisome proliferator-activated receptors, and perhaps a novel vascular...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e318192671d
更新日期:2009-04-01 00:00:00
abstract::The effects of R 56,865, a compound with unusual calcium antagonistic properties, on altered left ventricular (LV) diastolic properties were studied during pacing-induced ischemia in dogs with coronary stenosis. Severe coronary artery stenosis was produced on both the left anterior descending (LAD) and circumflex (Cx)...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199104000-00015
更新日期:1991-04-01 00:00:00
abstract::Drug-induced delayed cardiac repolarization is a recognized risk factor for proarrhythmia and is associated with block of IKr (the potassium current encoded by the human ether-a- go-go-related gene [hERG]). To evaluate the utility of 2 in vitro assays widely used to assess delayed repolarization, we compared the effec...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200403000-00007
更新日期:2004-03-01 00:00:00
abstract::Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities;...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181fd341c
更新日期:2011-01-01 00:00:00