Biomaterial Database

Beta-adrenergic stimulation and myocardial function in the failing heart. 2009

Ali El-Armouche, and Thomas Eschenhagen

Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Germany. a.el-armouche@uke.uni-hamburg.de

The sympathetic nervous system provides the most powerful stimulation of cardiac function, brought about via norepinephrine and epinephrine and their postsynaptic beta-adrenergic receptors. More than 30 years after the first use of practolol in patients with heart failure beta blockers are now the mainstay of the pharmacological treatment of chronic heart failure. Many aspects of their mechanism of action are well understood, but others remain unresolved. This review focuses on a number of questions that are key to further developments in the field. What accounts for and what is the role of beta-adrenergic desensitization, a hallmark of the failing heart? Is part of this adaptation predominantly beneficial and should therefore be reinforced, another part mainly maladaptive and therefore a target for antagonists? Which lessons can be drawn from studies in genetically engineered mice, which from (pharmaco) genetic studies? Finally, what are promising targets downstream of beta-adrenergic receptors that go beyond the current neurohumoral blockade?

UI	MeSH Term	Description	Entries
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010597	Pharmacogenetics	A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).	Pharmacogenomics
D011943	Receptors, Adrenergic, beta	One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.	Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D006333	Heart Failure	A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.	Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out