Beta-adrenoceptors in cardiac disease

The human heart contains both β1 and β-2-adrenoceptors; both mediated positive inotropic and chronotropic effects. In chronic heart failure, β-adrenoceptor number is reduced, presumably, by down-regulation by endogenous noradrenaline which is elevated due to increased sympathetic activity. Since the human heart contains only a few spare receptors for β-adrenoceptor-mediated positive inotropic effects and the amount of spare receptors declines in chronic heart failure, it is not surprising that the reduced β-adrenoceptor number is accompanied by decreased contractile responses to β-adrenoceptor agonists (including endogeneous catecholamines), and the extent of decrease in maximal inotropic response is more pronounced as the disease becomes more advanced. Moreover, in chronic heart failure myocardial Gi-protein, which inhibits cAMP formation, is increased, which might further contribute to the reduction in β-adrenoceptor-mediated effects. It appears that, at present, the best therapy for severe heart failure is a successful heart transplant, since in the transplanted heart β-adrenoceptor number and function seems to be noramalized. Moreover, the data currently available do not suggest any development of super- or subsensitivity of postsynaptic cardiac β-adrenoceptors in the transplanted human heart.