Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Germany.
Heart Fail Rev. 2009 Dec;14(4):225-41. doi: 10.1007/s10741-008-9132-8.
The sympathetic nervous system provides the most powerful stimulation of cardiac function, brought about via norepinephrine and epinephrine and their postsynaptic beta-adrenergic receptors. More than 30 years after the first use of practolol in patients with heart failure beta blockers are now the mainstay of the pharmacological treatment of chronic heart failure. Many aspects of their mechanism of action are well understood, but others remain unresolved. This review focuses on a number of questions that are key to further developments in the field. What accounts for and what is the role of beta-adrenergic desensitization, a hallmark of the failing heart? Is part of this adaptation predominantly beneficial and should therefore be reinforced, another part mainly maladaptive and therefore a target for antagonists? Which lessons can be drawn from studies in genetically engineered mice, which from (pharmaco) genetic studies? Finally, what are promising targets downstream of beta-adrenergic receptors that go beyond the current neurohumoral blockade?
交感神经系统通过去甲肾上腺素和肾上腺素及其突触后β肾上腺素能受体提供对心脏功能的最强刺激。在普萘洛尔首次用于心力衰竭患者 30 多年后，β受体阻滞剂现在是慢性心力衰竭药物治疗的主要方法。其作用机制的许多方面都得到了很好的理解，但其他方面仍未解决。这篇综述集中讨论了该领域进一步发展的一些关键问题。导致衰竭心脏β肾上腺素能受体失敏的原因是什么，其作用是什么？这种适应的一部分主要是有益的，因此应该得到加强，另一部分主要是适应不良的，因此是拮抗剂的靶点？从基因工程小鼠的研究中可以得到哪些经验教训，从（药物）遗传研究中又可以得到哪些经验教训？最后，β肾上腺素能受体下游有哪些有前途的靶点，可以超越当前的神经激素阻断？
