Erschienen in:
Circulation Research, 93 (2003) 10, Seite 896-906
Sprache:
Englisch
DOI:
10.1161/01.res.0000102042.83024.ca
ISSN:
0009-7330;
1524-4571
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>
This review addresses open questions about the role of β-adrenergic receptors in cardiac function and failure. Cardiomyocytes express all three β-adrenergic receptor subtypes—β
<jats:sub>1</jats:sub>
, β
<jats:sub>2</jats:sub>
, and, at least in some species, β
<jats:sub>3</jats:sub>
. The β
<jats:sub>1</jats:sub>
subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The β
<jats:sub>2</jats:sub>
subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the β
<jats:sub>1</jats:sub>
subtype. In heart failure, the sympathetic system is activated, cardiac β-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, β-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 β-adrenergic receptor system. Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps.
</jats:p>