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... Show moreAs 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 alpha- and beta-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 beta-ARs. However, information on the role of alpha-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular alpha(1)-ARs in HF using 5 databases for our search. All three alpha(1)-AR subtypes (alpha(1A), alpha(1B) and alpha(1D)) 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 alpha(1)-ARs. Conflicting findings arise from different studies concerning the influence that HF has on alpha(1)-AR expression and function; in contrast to beta-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular alpha(1)-ARs. Whether alpha(1)-ARs are a therapeutic target in HF remains a matter of debate. Show less