Gauthier Chantal, Rozec Bertrand, Manoury Boris, Balligand Jean-Luc
INSERM, UMR-915, l'institut du thorax, F-44000, Nantes, France.
Curr Heart Fail Rep. 2011 Sep;8(3):184-92. doi: 10.1007/s11897-011-0064-6.
Catecholamines play a key role in the regulation of cardiovascular function, classically through ß(1/2)-adrenoreceptors (AR) activation. After ß(3)-AR cloning in the late 1980s, convincing evidence for ß(3)-AR expression and function in cardiovascular tissues recently initiated a reexamination of their involvement in the pathophysiology of cardiovascular diseases. Their upregulation in diseased cardiovascular tissues and resistance to desensitization suggest they may be attractive therapeutic targets. They may substitute for inoperant ß(1/2)-AR to mediate vasodilation in diabetic or atherosclerotic vessels. In cardiac ventricle, their contractile effects are functionally antipathetic to those of ß(1/2)-AR; in normal heart, ß(3)-ARs may mediate a moderate negative inotropic effect, but in heart failure, it may protect against adverse effects of excessive catecholamine stimulation by action on excitation-contraction coupling, electrophysiology, or remodelling. Thus, prospective studies in animals and patients at different stages of heart failure should lead to identify the best therapeutic window to use ß(3)-AR agonists and/or antagonists.
儿茶酚胺在心血管功能调节中发挥关键作用，传统上是通过激活β(1/2)-肾上腺素能受体（AR）来实现的。20世纪80年代末β(3)-AR克隆成功后，近期有确凿证据表明心血管组织中存在β(3)-AR表达及功能，这引发了对其在心血管疾病病理生理学中作用的重新审视。它们在患病心血管组织中的上调以及对脱敏的抵抗表明它们可能是有吸引力的治疗靶点。它们可能替代无功能的β(1/2)-AR，在糖尿病或动脉粥样硬化血管中介导血管舒张。在心室中，它们的收缩作用在功能上与β(1/2)-AR相反；在正常心脏中，β(3)-AR可能介导适度的负性变力作用，但在心力衰竭时，它可能通过作用于兴奋-收缩偶联、电生理或重塑来防止儿茶酚胺过度刺激的不良影响。因此，针对心力衰竭不同阶段动物和患者的前瞻性研究应能确定使用β(3)-AR激动剂和/或拮抗剂的最佳治疗窗口。
