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 inflammation and apoptosis induced by ischemia-reperfusion in the cardioprotection by GSK-3beta inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8). Anaesthetized Sprague-Dawley rats underwent an open-chest procedure involving 30 min of myocardial ischemia and 6 h of reperfusion with or without TDZD-8 given at reperfusion. TDZD-8 reduced myocardial infarct size by nearly 43% (P < 0.05 vs. myocardial ischemia-reperfusion) and attenuated myeloperoxidase activity (21.80 +/- 1.07 U/100 mg tissue. vs. myocardial ischemia-reperfusion group, P < 0.05). Administration of TDZD-8 significantly suppressed nuclear factor kappa B (NF-kappaB) and p38 MAPK activation (P < 0.05 vs. myocardial ischemia-reperfusion) and the concentrations of the myocardial-derived cytokines tumor necrosis factor-alpha (TNF-alpha, 107.40 +/- 7.34 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05) and interleukin-6 (IL-6, 29.28 +/- 6.3 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05). Treatment with TDZD-8 also inhibited myocardial cell apoptosis compared with the myocardial ischemia-reperfusion group (12 +/- 1% vs. 22 +/- 2%, P < 0.05). Therefore, blocking this protein kinase activity may be a novel approach to the treatment of this condition, which is characterized by inflammation and apoptosis.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Gao HK,Yin Z,Zhou N,Feng XY,Gao F,Wang HCdoi
10.1097/FJC.0b013e318186a84dsubject
Has Abstractpub_date
2008-09-01 00:00:00pages
286-92issue
3eissn
0160-2446issn
1533-4023pii
00005344-200809000-00011journal_volume
52pub_type
杂志文章abstract::The serotonin (5-HT2A) antagonistic activities and the protective effect on laurate-induced peripheral vascular lesions of AT-1015, a novel 5-HT2 receptor antagonist, were investigated. In platelet aggregation, AT-1015 selectively inhibited in vitro 5-HT2A receptor-mediated aggregation, and the activity was almost equ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200004000-00002
更新日期:2000-04-01 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::Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 > nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199206203-00004
更新日期:1992-01-01 00:00:00
abstract::The beta-blocking activity of flestolol was established during increasing isoprenaline infusions and during graded physical exercise in conscious, chronically instrumented dogs. After a control cycle, flestolol was infused at three doses (1, 2.67, and 10 micrograms/kg/min). Flestolol has an extremely short half-life, ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199002000-00001
更新日期:1990-02-01 00:00:00
abstract::Hyperinsulinemia, lipid abnormalities, and impaired fibrinolytic capacity may accompany hypertension, and comprise the metabolic cardiovascular syndrome. They are all independent risk factors for coronary artery disease. Lifestyle modifications can reduce the coronary artery risk. Physical activity has been shown to i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1992-01-01 00:00:00
abstract::In helical strips of dog cerebral, coronary, mesenteric, and renal arteries treated with ONO3708, an inhibitor of vasoconstricting prostaglandin (PG) receptors, and previously contracted with serotonin, PGF2 alpha, PGD2 and epithio-methano thromboxane A2 (sTxA2), a TxA2 analog, caused a relaxation. The cerebral arteri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198803000-00014
更新日期:1988-03-01 00:00:00
abstract::To elucidate the role of potassium channel activation in muscarinic inhibition of atrial contractility, we studied the influence of K+ channel blockers on the effects of the muscarinic agonist carbachol in isolated guinea pig auricles. We tested BaCl2, tetraethylammoniumchloride (TEA), and 9-aminotetrahydroacridine (T...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198910000-00018
更新日期:1989-10-01 00:00:00
abstract::The new converting enzyme inhibitor cilazapril, or RO 31-2848, was evaluated in 14 healthy male volunteers. In a pilot study in two subjects, the inhibiting capacity of single oral doses of 5 and 10 mg on the pressure and heart rate response to exogenous angiotensin I was assessed. Both doses reduced the blood pressur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Platelet GPIIb/IIIa antagonists are not only used to prevent platelet aggregation, but also in combination with thrombolytic agents for the treatment of coronary thrombi. Recent data indicate a potential of abciximab alone to dissolve thrombi in vivo. We investigated the potential of abciximab, eptifibatide, and tirof...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200304000-00011
更新日期:2003-04-01 00:00:00
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
更新日期:2015-02-01 00:00:00
abstract::The maximal increases in heart rate produced by intravenous xamoterol in anaesthetized cats and rats are less than that of (-)-isoprenaline. In cats, blood pressure was slightly raised, while in rats, supramaximal cardiac-stimulant doses produced reductions in blood pressure. In anaesthetized guinea pigs, cardiac-stim...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198603000-00014
更新日期:1986-03-01 00:00:00
abstract::Endothelin-1 (ET-1) produced by vascular endothelial cells has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMCs) in vivo, exerting a variety of short- and long-term effects. Although some of the in vitro ET-1-mediated effects are related to growth-promoting events, the physiological sig...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199204002-00011
更新日期:1992-01-01 00:00:00
abstract::Essential hypertension is now considered a disease of pressure regulation implicating a multiplicity of physiological mechanisms. It is probably genetically predisposed and is associated with altered sensitivity to the sodium ion and a more than chance association with other clinical diseases. New concepts are emergin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::We undertook a systematic comparison of the effects of diltiazem and nifedipine and a nonspecific vasodilator, sodium nitroprusside, on renal perfusion, function, and activation of potentially relevant neurohormonal systems in the anesthetized dog. These agents were employed to reduce blood pressure to two levels, a m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198601000-00006
更新日期:1986-01-01 00:00:00
abstract::Coronary hemodynamics (blood flow, coronary reserve, myocardial oxygen consumption) were analyzed in both experimental and clinical hypertension. Significantly reduced coronary reserve was found in hypertensive patients with left ventricular hypertrophy. Medial hypertrophy of small coronary vessels associated with a m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The purpose of this study was to compare the acute hypotensive efficacy of different types of inhibitor of the renin-angiotensin system. A renin inhibitor (RI), CGP 44,099 A, a converting enzyme inhibitor (CEI), enalaprilat, a peptidic angiotensin II (Ang II) antagonist, [Sar1, Ile8]Ang II (P-Ang IIA), and a nonpeptid...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199016004-00013
更新日期:1990-01-01 00:00:00
abstract::We have previously demonstrated that endothelin-1 (ET-1) is essential to the development of neural crest-derived craniofacial and cardiovascular structures. In this study we evaluated the intrauterine growth and development of the thyroid and thymus glands in Edn1-/- homozygous mice. Edn1-/- homozygous mice were small...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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
更新日期:2007-06-01 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::We studied the influence of prostacyclin (PGI2) on the contractile performance of isolated mammalian ventricular muscle. PGI2 had no direct influence on myocardial contractility, as evidenced by experiments on single cardiac cells and papillary muscle. Moreover, PGI2 did not interfere with the inotropic action of isop...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198509000-00025
更新日期:1985-09-01 00:00:00
abstract::The effects of olprinone (0.2 microg/kg per minute, i.v.) on cerebral blood flow were examined using technetium-99m-ethyl cysteinate dimer (99mTc-ECD) brain single-photon emission computed tomography in 14 stroke patients (69.0 +/- 5.6 years) and 12 normal subjects (68.1 +/- 6.2 years). The regional cerebral blood flo...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-200104000-00004
更新日期:2001-04-01 00:00:00
abstract::The binding of [3H]ketanserin and [125I]BE 2254 [( beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone) was characterized in human brain cortex membranes. As observed in saturation experiments, [3H]ketanserin (a reportedly selective serotonin 5-HT2 ligand) and [125I]BE 2254 (a selective alpha 1-adrenergic antagonists) la...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group....
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199007000-00012
更新日期:1990-07-01 00:00:00
abstract::The effects on blood lipids and uric acid of six different antihypertensive drugs used alone, and of five different combinations of two antihypertensive drugs, are reported here. Prazosin significantly lowered serum low density lipoprotein and very low density lipoprotein (LDL + VLDL) cholesterol and total triglycerid...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Vasoconstrictor responses to intraluminal and extraluminal 5-hydroxytryptamine (5-HT) were studied in isolated mesenteric resistance arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Third-order branches of mesenteric arteries were dissected free and mounted on glass cannulae in organ cha...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199108000-00015
更新日期:1991-08-01 00:00:00
abstract::This selective review of a few of the advances made in recent years indicates that we are entering a new era in cardiovascular pharmacology. Drugs with novel mechanisms of action, and modifications of existing drugs, are being developed in constantly increasing numbers. The clinical evaluation of these drugs will be a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection wa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Hypertension is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypert...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31824f9174
更新日期:2012-06-01 00:00:00
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::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