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 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.
Molenaar
Peter
P
Discipline of Medicine, The University of Queensland, The Prince Charles Hospital Chermside, Queensland 4032, Australia. p.molennar@mailbox.uq.edu.au
Parsonage
William A
WA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta