Molenaar Peter, Parsonage William A
Discipline of Medicine, The University of Queensland, The Prince Charles Hospital Chermside, Queensland 4032, Australia.
Trends Pharmacol Sci. 2005 Jul;26(7):368-75. doi: 10.1016/j.tips.2005.05.005.
beta-Adrenoceptor antagonists have revolutionized the management of heart failure in humans. However, fundamental questions remain concerning their use. Currently, there is considerable debate about the role of beta2-adrenoceptors in heart failure and whether incremental clinical benefit can be obtained by blockade of beta2-adrenoceptors in addition to beta1-adrenoceptors. Polymorphic forms of beta1- and beta2-adrenoceptors exist, which might contribute to the variable clinical outcomes that are observed with beta-adrenoceptor antagonists. There is evidence for a low-affinity state of beta1-adrenoceptors and ventricular beta3-adrenoceptors, and these are discussed in the context of heart failure. Finally, there is seemingly paradoxical evidence that restoration and normalization of the beta-adrenoceptor system is beneficial in animal models of heart failure. We reconcile this view with the current clinical use and proven benefit of beta-adrenoceptor antagonists.
β-肾上腺素能受体拮抗剂彻底改变了人类心力衰竭的治疗方法。然而，关于它们的使用仍存在一些基本问题。目前，关于β2-肾上腺素能受体在心力衰竭中的作用以及除β1-肾上腺素能受体阻断外，阻断β2-肾上腺素能受体是否能获得额外的临床益处，存在相当大的争议。β1-和β2-肾上腺素能受体存在多态性形式，这可能导致使用β-肾上腺素能受体拮抗剂时观察到的临床结果存在差异。有证据表明β1-肾上腺素能受体和心室β3-肾上腺素能受体存在低亲和力状态，并在心力衰竭的背景下进行了讨论。最后，有看似矛盾的证据表明，β-肾上腺素能受体系统的恢复和正常化在心力衰竭动物模型中是有益的。我们将这一观点与β-肾上腺素能受体拮抗剂目前的临床应用和已证实的益处进行了协调。
