Cardiovascular Molecular & Therapeutics Translational Research Group, Northside Clinical School of Medicine, University of Queensland, The Prince Charles Hospital, Chermside, QLD, Australia.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Handb Exp Pharmacol. 2024;285:247-295. doi: 10.1007/164_2024_720.
β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β-AR, β-AR, β-AR are localized to the human heart. Activation of β-AR and β-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of β-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of β-AR is critical in the pathogenesis of cardiac arrhythmias while activation of β-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of β-AR in cardiovascular disease, particularly arrhythmia generation. All β-blockers used therapeutically to treat cardiovascular disease block β-AR with variable blockade of β-AR depending on relative affinity for β-AR vs β-AR. Since the introduction of β-blockers into clinical practice in 1965, β-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. β-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. β-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The β-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other β-blockers and is used successfully in the treatment of heart failure. The discovery of β-AR in human heart created interest in the role of β-AR in heart failure but has not resulted in therapeutics at this stage.
β-肾上腺素受体（β-ARs）为治疗心血管疾病提供了一个重要的治疗靶点。三种β-AR，β-1-AR、β-2-AR 和 β-3-AR，定位于人体心脏。β-AR 和 β-2-AR 的激活可增加心率、收缩力（变力性），从而增加心输出量以满足生理需求。然而，在疾病中，β-AR 的慢性过度激活导致疾病的进展（例如心力衰竭），其机制为病理性肥大、不良重构和细胞过早死亡。此外，β-AR 的激活在心律失常的发病机制中至关重要，而β-3-AR 的激活直接影响血压止血。人们越来越意识到β-AR 在心血管疾病中的作用，尤其是心律失常的发生。所有用于治疗心血管疾病的β-受体阻滞剂都通过不同程度地阻断β-1-AR 和 β-2-AR 来阻断β-AR，具体取决于对β-1-AR 和 β-2-AR 的相对亲和力。自 1965 年β-受体阻滞剂引入临床实践以来，已经对具有不同特性的β-受体阻滞剂进行了试验、使用和评估，从而更好地了解了它们在各种心血管疾病中的治疗效果和耐受性。具有内在拟交感神经活性（ISA）的β-受体阻滞剂，即也能激活受体的β-受体阻滞剂，过去曾用于心肌梗死后的治疗，但在心力衰竭中的应用有限。β-受体阻滞剂卡维地洛由于其与其他β-受体阻滞剂的许多特性不同而备受关注，并且在心力衰竭的治疗中成功使用。β-3-AR 在人类心脏中的发现引起了人们对其在心力衰竭中的作用的兴趣，但在现阶段尚未开发出治疗药物。
