| Summary: | As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α<sub>1</sub>-ARs in HF using 5 databases for our search. All three α<sub>1</sub>-AR subtypes (α<sub>1A</sub>, α<sub>1B</sub> and α<sub>1D</sub>) are expressed in human and animal hearts and blood vessels in a tissue-dependent manner. We summarize the changes observed in HF regarding the density, signaling and responses of α<sub>1</sub>-ARs. Conflicting findings arise from different studies concerning the influence that HF has on α<sub>1</sub>-AR expression and function; in contrast to β-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular α<sub>1</sub>-ARs. Whether α<sub>1</sub>-ARs are a therapeutic target in HF remains a matter of debate.
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