| Background Heart failure (HF) is a complicated clinical syndrome.According to domestic informations,HF cases occupy for 20% in hospitalization of cardiovascular diseases,and it's mortality rate is about 40%.In pediatrics,HF is a frequent dangerous emergency case and often result in death.For half a century,experts have been studing much about HF on pathogenesis,but the pathogenesis of chronic HF is still not completely understood and it's still difficult to cure it.So it's necessary to further explore the pathogenesis and effective medicine of HF. There is great association between the level of Ca2+ and cardiac systolic and diastolic function .Ryanodine receptors (RyRs) are cardiac intracellular ion channels that provide a pathway for releasing of Ca2+ from the sarcoplasmic reticulum (SR)/endoplasmic reticulum into the cytosol. The release of intracellular stores of Ca2+ occurs in virtually all types of cells as a means of amplifying external signals that modulate intracellular signaling events. In cardiac myocytes, type 2 RyRs (RyR2s) are activated during excitation-contraction (E-C) coupling by Ca2+-induced Ca2+ release (CICR) triggered by Ca2+ influx across the sarcolemma. ?-adrenergic receptor (?-AR) blockade can improve cardiac contractility and prolongs survival in patients with HF have been demonstrated by a lot of clinical trials; however, the mechanisms underlying these favorable responses are still not completely understood. Stress-induced activation of the sympathetic nervous system results in protein kinase A (PKA)-mediated phosphorylation of the calcium (Ca2+) release channel/cardiac RyR2 , required for cardiac excitation-contraction coupling, activating the RyR2 channel, and increasing cardiac contractility. The hyperadrenergic state of heart failure results in leaky RyR2 channels attributable to PKA hyperphosphorylation and depletion of the stabilizing FK506 binding protein, FKBP12.6. Experts tested the hypothesis that improved cardiac muscle function attributable to ?-AR blockade is associated with restoration of normal RyR2 channel function in patients with heart failure. Taken together, many data indicated that systemic ? -adrenergic blockade can reverse the defects in the structure and function of RyR2 observed in failing hearts.Regulation of Ca2+ homeostasis in cardiomyocytes is a complex process that requires the integrated function of multiple Ca2+-handling molecules. RyR2 plays a key role in cardiac excitation-contraction coupling, and data from our laboratory and others suggest that dysregulation of SR Ca2+ release via RyR2 could contribute to defects in Ca2+ signaling in failing hearts. Many studies show that β-adrenergic blockade can restore cardiac function in patients with HF. We have proposed that hyperphosphorylated RyR2 depleted of FKBP12.6 could contribute to a reduction in SR Ca2+ content and uncoupling of RyR2. The chronic alterations in RyR2 function could contribute to a reduction in excitation-contraction coupling gain and decreased Ca2+ transients in failing hearts and possibly produce Ca2+ release in diastolic period that can trigger delayed afterdepolarizations and initiate fatal ventricular cardiac arrhythmias (sudden cardiac death). In agreement with these possibilities, recent studies have shown either a reduction in SR Ca2+ content, decreased Ca2+ transients, or decreased excitation-contraction coupling gain incardiomyocytes from failing hearts as well as reduced levels of FKBP12.6 in the RyR2 macromolecular complex.There are less reports about RyR2 in pediatric HF and the effect of ? –AR blockade on RyR so far. Objective To investigate the change of RyR in junior mouse with HF and the effect of ?-adrenoreceptor blocker on RyR in HF. Methods The animal model of congestive heart failure was established by constriction of abdominal aorta.The mouse of five weeks old were randomly divided into 3 groups: (1)HF group without treated (n=20); (2)HF group treated with carvedilol(n=20) ; (3)Sham-operated group(n=20).Carvedilol was administered through direct gastric g...
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