The biogenic amine, histamine, is found predominantly in mast cells, as well as specific histaminergic neurons. Histamine exerts its many and varied actions via four G-protein-coupled receptors numbered one through four. Histamine has multiple effects on cardiac physiology, mainly via the histamine 1 and 2 receptors, which on a simplified level have opposing effects on heart rate, force of contraction, and coronary vasculature function. In heart failure, the actions of the histamine receptors are complex, the histamine 1 receptor appears to have detrimental actions predominantly in the coronary vasculature, while the histamine 2 receptor mediates adverse effects on cardiac remodeling via actions on cardiomyocytes, fibroblasts, and even endothelial cells. Conversely, there is growing evidence that the histamine 3 receptor exerts protective actions when activated. Little is known about the histamine 4 receptor in heart failure. Targeting histamine receptors as a therapeutic approach for heart failure is an important area of investigation given the over-the-counter access to many compounds targeting these receptors, and thus the relatively straight forward possibility of drug repurposing. In this review, we briefly describe histamine receptor signaling and the actions of each histamine receptor in normal cardiac physiology, before describing in more detail the known role of each histamine receptor in adverse cardiac remodeling and heart failure. This includes information from both clinical studies and experimental animal models. It is the goal of this review article to bring more focus to the possibility of targeting histamine receptors as therapy for heart failure.

生物胺组胺主要存在于肥大细胞以及特定的组胺能神经元中。组胺通过编号为 1 至 4 的四种 G 蛋白偶联受体发挥其多种不同的作用。组胺对心脏生理有多种作用，主要是通过组胺 1 和 2 受体，在简化的层面上，它们对心率、收缩力和冠状血管功能具有相反的作用。在心力衰竭中，组胺受体的作用是复杂的，组胺 1 受体似乎主要在冠状血管系统中具有有害作用，而组胺 2 受体通过对心肌细胞、成纤维细胞甚至内皮细胞的作用介导对心脏重塑的不利影响. 反过来，越来越多的证据表明组胺 3 受体在被激活时会发挥保护作用。关于心力衰竭中的组胺 4 受体知之甚少。将组胺受体作为心力衰竭的治疗方法是一个重要的研究领域，因为许多针对这些受体的化合物可以通过非处方药获得，因此药物再利用的可能性相对直接。在这篇综述中，我们简要描述了组胺受体信号传导和每种组胺受体在正常心脏生理中的作用，然后更详细地描述了每种组胺受体在不良心脏重塑和心力衰竭中的已知作用。这包括来自临床研究和实验动物模型的信息。