Fundamental considerations of beta-adrenoceptor subtypes in human heart failure

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 beta(2)-adrenoceptors in heart failure and whether incremental clinical benefit can be obtained by blockade of beta(2)-adrenoceptors in addition to beta(1)-adrenoceptors. Polymorphic forms of beta(1)- and beta(2)-adrenoceptors exist, which might contribute to the variable clinical outcomes that are observed with P-adrenoceptor antagonists. There is evidence for a low-affinity state of beta(1)-adrenoceptors and ventricular beta(3)-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.