Affiliation:
1. From the Institute of Pharmacology (M.J.L., S.E.), Wuerzburg, Germany; Institute of Experimental and Clinical Pharmacology (T.E.), Universitaetsklinikum Hamburg-Eppendorf, Germany.
Abstract
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
1
, β
2
, and, at least in some species, β
3
. The β
1
subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The β
2
subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the β
1
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
666 articles.
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