Zusammenfassung
This review addresses open questions about the role of beta-adrenergic
receptors in cardiac function and failure. Cardiomyocytes express
all three beta-adrenergic receptor subtypes-beta1, beta2, and, at
least in some species, beta3. The beta1 subtype is the most prominent
one and is mainly responsible for positive chronotropic and inotropic
effects of catecholamines. The beta2 subtype also increases cardiac
function, but its ability to activate nonclassical signaling pathways
suggests a function distinct from the beta1 subtype. In heart failure,
the sympathetic system is activated, cardiac beta-receptor number
and function are decreased, and downstream mechanisms are altered.
However, in spite of a wealth of data, we still do not know whether
and to what extent these alterations are adaptive/protective or detrimental,
or both. Clinically, beta-adrenergic antagonists represent the most
important advance in heart failure therapy, but it is still debated
whether they act by blocking or by resensitizing the beta-adrenergic
receptor system. Newer experimental therapeutic strategies aim at
the receptor desensitization machinery and at downstream signaling
steps.
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