Abstract:
OBJECTIVE:Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we assessed the role of presynaptic adenosine-receptors and alpha2-adrenoceptors in neuronal stunning. METHODS AND RESULTS:Exocytotic NE release was induced by two electrical field stimulations (S(1) and S(2)) in isolated perfused rat hearts. S(1) was performed under baseline conditions and S(2) either during or following intervention. Results are expressed as mean S(2)/S(1) ratios+/-S.E.M. Stepwise increase of global ischemic periods (10, 20, and 30 min) induced a progressive suppression of NE release in the postischemic hearts, which was reversible during reperfusion. Both the degree and duration of NE suppression was dependent on the extent of the preceding ischemic period. Following 10-min ischemia complete recovery of NE release was achieved after 5-min reperfusion (1.07+/-0.12), whereas 5-min reperfusion did not restore NE release after 30 min (0.36+/-0.07) of ischemia. The adenosine-receptor antagonists 8-phenyltheophylline (8-PT; non-selective) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; adenosine A1-receptor subtype selective) significantly increased NE release after 30-min ischemia and 5-min reperfusion (0.78+/-0.06 and 0.64+/-0.07), while in the same experimental protocol blockade of alpha2-adrenoceptors by yohimbine failed to restore the postischemic release (0.24+/-0.06). In non-ischemic hearts the adenosine analogue R(-)N(6)-(2-phenylisopropyl)adenosine (R-PIA) resulted in a marked suppression of NE release (0.61+/-0.07). The inhibitory effect of R-PIA and 2-chloro-N(6)-cyclopentyladenosine (CCPA; adenosine A1-receptor subtype selective agonist) persisted 5 min after cessation of R-PIA (0.62+/-0.05) and CCPA (0.58+/-0.04). Activation of alpha2-adrenoceptors by 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304) also caused a reduction of NE release (0.50+/-0.02), but the release increased to control levels 5 min after cessation of UK 14,304 (0.90+/-0.06). CONCLUSIONS:The results establish the phenomenon of neuronal stunning in terms of a postischemic suppression of exocytotic NE release and provide evidence that neuronal stunning is mediated by endogenous adenosine through activation of presynaptic adenosine A1-receptors.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Burgdorf C,Richardt D,Kurz T,Seyfarth M,Jain D,Katus HA,Richardt Gdoi
10.1016/s0008-6363(00)00309-6subject
Has Abstractpub_date
2001-03-01 00:00:00pages
713-20issue
4eissn
0008-6363issn
1755-3245pii
S0008636300003096journal_volume
49pub_type
杂志文章abstract:AIMS:This study aimed at characterizing expression and the functional role of the Gjb6 gene, encoding for connexin 30 (Cx30) protein, in the adult mouse heart. METHODS AND RESULTS:The expression of the Gjb6 gene in the mouse heart was investigated by RT-PCR and sequencing of amplified cDNA fragments. The sites of Gjb6...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp280
更新日期:2010-01-01 00:00:00
abstract:AIMS:As cardiovascular disease is characterized by reduced nitric oxide bioavailability, our aim was to determine the impact of this change on the mechanism underlying vascular tone of pressurized arteries in vitro and in vivo. METHODS AND RESULTS:We used pressurized cerebral and mesenteric arteries in vitro and skele...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt043
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVES:Responses to EDHF are usually characterised in the presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors. The contribution of NO to endothelium-dependent relaxation in the presence of NOS inhibitors was assessed using NO scavengers with the objective of testing (i) whether any residual ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00611-9
更新日期:2003-01-01 00:00:00
abstract:AIMS:Herpes virus entry mediator (HVEM) is considered to be a molecular 'switch' for immune responses, and a role in immune modification has been reported. The aim of this study was to assess whether HVEM-mediated immune suppression could protect against experimental autoimmune myocarditis (EAM) induced by myosin. MET...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp219
更新日期:2009-12-01 00:00:00
abstract:AIM:Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm069
更新日期:2008-02-01 00:00:00
abstract:AIMS:Hypercholesterolaemia and myeloperoxidase (MPO) overexpression are two well-recognized risk factors for ischaemic heart disease. Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists have recently been shown to reduce ischaemic heart injury in hypercholesterolaemic animals. However, whether PPARgam...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn308
更新日期:2009-02-01 00:00:00
abstract::The 'master regulatory factors' that position at the top of the genetic hierarchy of lineage determination have been a focus of intense interest, and have been investigated in various systems. Etv2/Etsrp71/ER71 is such a factor that is both necessary and sufficient for the development of haematopoietic and endothelial...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvx133
更新日期:2017-09-01 00:00:00
abstract:OBJECTIVE:In isolated cardiac preparations of non-failing hearts from different species, including man, there is a positive force-frequency relation which is reversed into a negative relation in preparation from failing hearts. Whether or not such relations between ventricular function and heart rate hold true in the i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00246-0
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:The adhesive interaction of monocytes and endothelial cells has been implicated as a regulatory signal in the cell activation that is involved in the pathogenesis of atherosclerosis. We investigated the effect of monocyte-endothelial cell interaction on the expression of adhesion molecules, intercellular adhe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00085-5
更新日期:1996-08-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate the effects of long-term treatment with an alpha 1 blocker, bunazosin hydrochloride, on blood pressure, heart weight, myocardial contractility, and ventricular myosin isoenzyme pattern in spontaneously hypertensive rats (SHR). DESIGN:Bunazosin hydrochloride was given orally i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.7.565
更新日期:1991-07-01 00:00:00
abstract::Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, t...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs111
更新日期:2012-07-15 00:00:00
abstract:OBJECTIVES:The purpose of this study was to investigate the changes in beta-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:OBJECTIVES:Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract:Aims:Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy167
更新日期:2018-11-01 00:00:00
abstract::Numerous epidemiological studies documented an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and the extent of atherosclerotic disease. However, clinical interventions targeting HDL cholesterol failed to show clinical benefits with respect to cardiovascular risk reduction, sugge...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu136
更新日期:2014-08-01 00:00:00
abstract::Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy006
更新日期:2018-03-15 00:00:00
abstract:OBJECTIVES:We studied the effects of chronic left coronary artery ligation on cardiac structure and function in the mouse. METHODS:Morphometric studies of the left ventricle were performed in coronary artery-ligated and sham-operated animals at one, two, three and five weeks after surgery. The fraction of DNA-synthesi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00216-8
更新日期:1999-03-01 00:00:00
abstract:AIMS:It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis tha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr167
更新日期:2011-11-01 00:00:00
abstract::Intracellular acidosis exerts substantial effects on the contractile performance of the heart. Soon after the onset of acidosis, contractility diminishes, largely due to a decrease in myofilament Ca(2+) responsiveness. This decrease in contractility is followed by a progressive recovery that occurs despite the persist...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.12.002
更新日期:2007-03-01 00:00:00
abstract::An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.95
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to examine the effect of ischaemia on vascular responses to endothelium-dependent and endothelium-independent vasodilators and on vasoconstrictor responses. Furthermore, the ability of preconditioning to prevent ischaemia-induced changes in vascular reactivity was examined in the rat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00167-8
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE:In pigs, the infarct size (IS) reduction achieved by a strong preconditioning stimulus (IPs) of 10 min ischemia and 15 min reperfusion is greater than that by a weaker preconditioning stimulus (IPw) of 3 min ischemia and 15 min reperfusion. The cardioprotection achieved by IPw is completely abolished by block...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00505-3
更新日期:2002-08-15 00:00:00
abstract:AIMS:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily of ligand-activated transcriptional regulators. PPARdelta has an established role in metabolism, wound healing, and angiogenesis. However, little is known about its function in endothelial homeostasis. We investigat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp365
更新日期:2010-03-01 00:00:00
abstract::Therapeutic neovascularization for cardiovascular ischemia is a promising avenue in spite of disappointing early clinical trial results. The concept of three different mechanisms of neovascularization has served to define potential therapeutic targets such as vascular remodeling and stem cell recruitment, but it is an...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.11.020
更新日期:2005-02-15 00:00:00
abstract::Stroke, ischaemic stroke and subtypes of ischaemic stroke display substantial heritability. When compared with related vascular conditions, the number of established risk loci reaching genome-wide significance for association with stroke is still in the lower range, particularly for aetiological stroke subtypes such a...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy068
更新日期:2018-07-15 00:00:00
abstract:OBJECTIVE:The primary aim of this study was to investigate whether activation of Na influx via voltage-gated Na channels can elevate sub-sarcolemmal ('fuzzy-space') [Na] and transiently activate Na/K pump current (I(p)). METHODS AND RESULTS:Initially, Na/K pump activity was characterised in whole-cell voltage-clamped ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00645-4
更新日期:2003-03-15 00:00:00
abstract::Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of mat...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.06.006
更新日期:2004-10-01 00:00:00
abstract:AIM:Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardiu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv167
更新日期:2015-07-15 00:00:00
abstract:OBJECTIVE:The factors involved in restenosis after balloon angioplasty are poorly characterized but the local concentration of the potent mitogens angiotensin II (AII) and thrombin is known to be increased at sites of vascular injury. We investigated the possibility of a synergistic interaction between AII and thrombin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00296-4
更新日期:1998-04-01 00:00:00
abstract:AIMS:Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:Mice ...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt235
更新日期:2014-01-01 00:00:00