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Abstract. At present, nine adrenoceptor (AR) subtypes have been identified: α 1A -, α 1B -, α 1D -, α 2A -, α 2B -, α 2C -, β 1 -, β 2 -, and β 3 AR. In the human heart, β 1 -and β 2 AR are the most powerful physiologic mechanism to acutely increase cardiac performance. Changes in βAR play an important role in chronic heart failure (CHF). Thus, due to increased sympathetic activity in CHF, βAR are chronically (over)stimulated, and that results in β 1 AR desensitization and alterations of down-stream mechanisms. However, several questions remain open: What is the role of β 2 AR in CHF? What is the role of increases in cardiac G i -protein in CHF? Do increases in G-protein-coupled receptor kinase (GRK)s play a role in CHF? Does βAR-blocker treatment cause its beneficial effects in CHF, at least partly, by reducing GRK-activity? In this review these aspects of cardiac AR pharmacology in CHF are discussed. In addition, new insights into the functional importance of β 1 -and β 2 AR gene polymorphisms are discussed. At present it seems that for cardiovascular diseases, βAR polymorphisms do not play a role as disease-causing genes; however, they might be risk factors, might modify disease, and / or might influence progression of disease. Furthermore, βAR polymorphisms might influence drug responses. Thus, evidence has accumulated that a β 1 AR polymorphism (the Arg389Gly β 1 AR) may affect the response to βAR-blocker treatment.

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The sympathetic and parasympathetic nervous system play a powerful role in controlling cardiac function by activating adrenergic and muscarinic receptors. In the human heart there exist alpha1-, beta1- and beta2-adrenoceptors and M2-muscarinic receptors and possibly also (prejunctional) alpha2-adrenoceptors. Beta1- and beta2-adrenoceptors are quite evenly distributed in the human heart while M2-receptors are heterogeneously distributed (more receptors in atria than in ventricles). Stimulation of beta1- and beta2-adrenoceptors causes increases in heart rate and force of contraction while stimulation of M2-receptors decreases heart rate (directly in atria) and force of contraction (indirectly in ventricles). Pathological situations (such as heart failure) or pharmacological interventions (for example, beta-blocker treatment) can alter the distribution of beta1- and beta2-adrenoceptors in the human heart, while M2-receptors are only marginally affected. On the other hand, relatively little is known on distribution and functional role of alpha1- and alpha2-adrenoceptor subtypes in the human heart.