Abstract:
:Growing evidence exists that ATP-sensitive mitochondrial potassium channels (MitoKATP channel) are a major contributor to the cardiac protection against ischemia. Given the importance of mitochondria in the cardiac cell, we tested whether the potent and specific opener of the MitoKATP channel diazoxide attenuates the lethal injury associated with Ca2+overload. The specific aims of this study were to test whether protection by diazoxide is mediated by MitoKATP channels; whether diazoxide mimics the effects of Ca2+ preconditioning; and whether diazoxide reduces Ca2+ paradox (PD) injury via protein kinase C (PKC) signaling pathways. Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 minutes of Ca2+ depletion followed by 10 minutes of Ca2+ repletion). The effects of the MitoKATP channel and other interventions on functional, biochemical, and pathological changes in hearts subjected to Ca2+ PD were assessed. In hearts treated with 80 micromol/L diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly preserved after Ca2+ PD; peak lactate dehydrogenase release was also significantly decreased, although ATP content was less depleted. The cellular structures were well preserved, including mitochondria and intercalated disks in diazoxide-treated hearts compared with nontreated Ca2+ PD hearts. The salutary effects of diazoxide on the Ca2+ PD injury were similar to those in hearts that underwent Ca2+ preconditioning or pretreatment with phorbol 12-myristate 13-acetate before Ca2+ PD. The addition of sodium 5-hydroxydecanoate, a specific MitoKATP channel inhibitor, or chelerythrine chloride, a PKC inhibitor, during diazoxide pretreatment completely abolished the beneficial effects of diazoxide on the Ca2+ PD. Blockade of Ca2+ entry during diazoxide treatment by inhibiting L-type Ca2+ channel with verapamil or nifedipine also completely reversed the beneficial effects of diazoxide on the Ca2+ PD. PKC-delta was translocated to the mitochondria, intercalated disks, and nuclei of myocytes in diazoxide-pretreated hearts, and PKC-alpha and PKC-epsilon were translocated to sarcolemma and intercalated disks, respectively. This study suggests that the effect of the MitoKATP channel is mediated by PKC-mediated signaling pathway.
journal_name
Circ Resjournal_title
Circulation researchauthors
Wang Y,Ashraf Mdoi
10.1161/01.res.84.10.1156subject
Has Abstractpub_date
1999-05-28 00:00:00pages
1156-65issue
10eissn
0009-7330issn
1524-4571journal_volume
84pub_type
杂志文章abstract::The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.6.1097
更新日期:1994-06-01 00:00:00
abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1801.096264
更新日期:2001-09-14 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.39.2.245
更新日期:1976-08-01 00:00:00
abstract:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...
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doi:10.1161/CIRCRESAHA.115.304351
更新日期:2014-08-15 00:00:00
abstract::The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellul...
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pub_type: 杂志文章
doi:10.1161/01.res.62.2.358
更新日期:1988-02-01 00:00:00
abstract::In intact porcine aorta, endothelium-derived nitric oxide released on thrombin stimulation inhibits the concomitant production of endothelin. Experiments were designed to examine the effect of hirudin (which inactivates thrombin) and the nitrovasodilators nitroglycerin and 3-morpholinosydnonimine on the spontaneous an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1768
更新日期:1991-06-01 00:00:00
abstract::The aims of the current study were to examine the efficacy of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of nitric oxide (NO), muscarinic receptors, and ATP-sensitive K+ (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 min...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.6.1193
更新日期:1993-12-01 00:00:00
abstract::The release of acetylcholine from autonomic nerves in those tissues that receive a cholinergic innervation is widely believed to dilate blood vessels. Exogenously administered acetylcholine in vivo does dilate vascular beds and produce hypotension; however, this latter effect is indirect and probably the result of lib...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:1989-08-01 00:00:00
abstract::Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. These studies have revealed...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.161778
更新日期:2008-02-29 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.6.1087
更新日期:1995-12-01 00:00:00
abstract::G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000247932.71270.2c
更新日期:2006-10-27 00:00:00
abstract::Effects of blood flow on the production of prostacyclin (PGI2) were examined in the canine femoral artery perfused ex vivo. Each artery was perfused in situ with medium 199, under conditions of simulated blood flow. To simulate the normal and abnormal blood flow waveforms at the same mean flow rate, we developed a flo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.4.1095
更新日期:1991-04-01 00:00:00
abstract::The beta-adrenergic agonist isoproterenol stimulates immunoreactive atrial natriuretic peptide (IR-ANP) secretion by superfused rat atria in vitro. beta-Adrenergic agonists alter the cellular handling of calcium, which culminates in a rise in the systolic calcium concentration. This is achieved by increasing calcium i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.3.600
更新日期:1989-09-01 00:00:00
abstract::The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.5.1302
更新日期:1991-05-01 00:00:00
abstract::As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.2.245
更新日期:1981-02-01 00:00:00
abstract:RATIONALE:Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305347
更新日期:2015-04-10 00:00:00
abstract:RATIONALE:Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date. OBJECTIVE:To explore the temporal rel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317950
更新日期:2020-12-04 00:00:00
abstract::To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.5.1161
更新日期:1989-11-01 00:00:00
abstract::Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.1.218
更新日期:1990-01-01 00:00:00
abstract::Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been sho...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.172619
更新日期:2008-08-15 00:00:00
abstract::Inherited restrictive cardiomyopathy (RCM) is a debilitating disease characterized by a stiff heart with impaired ventricular relaxation. Mutations in cardiac troponin I (cTnI) were identified as causal for RCM. Acute genetic engineering of adult cardiac myocytes was used to identify primary structure/function effects...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000268412.34364.50
更新日期:2007-05-25 00:00:00
abstract::Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.1.42
更新日期:1987-07-01 00:00:00
abstract::Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.735
更新日期:1995-10-01 00:00:00
abstract::Reductions in fluid shear stress produce endothelium-dependent vasoconstriction and promote neointimal hyperplasia, but the intracellular signaling mechanisms involved in these processes are poorly understood. To examine whether decreases in fluid shear stress affect endothelial cytosolic pH, carboxy-seminaphthorhodaf...
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更新日期:1998-04-20 00:00:00
abstract::A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1190
更新日期:1989-06-01 00:00:00
abstract::The sarcolemmal Na+-Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism in cardiac myocytes and is thus essential for the regulation of Ca2+ homeostasis and contractile function. A cytosolic region (f-loop) of the protein mediates regulation of NCX function by intracellular factors including inhibition by exchan...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000151334.48676.68
更新日期:2005-01-07 00:00:00
abstract::High-density lipoprotein (HDL) is a complex mixture of lipoproteins that is associated with many minor proteins and lipids that influence the function of HDL. Although HDL is a promising marker and potential therapeutic target based on its epidemiological data and the effects of healthy HDL in vitro in endothelial cel...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2014-01-03 00:00:00
abstract::Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1301.092508
更新日期:2001-07-06 00:00:00
abstract::The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.3.409
更新日期:1987-09-01 00:00:00
abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.3.393
更新日期:1986-03-01 00:00:00