Beta-adrenoceptors in cardiac disease

• Published in: Pharmacology & therapeutics (Oxford) Vol. 60; no. 3; pp. 405 - 430
• Main Author: Brodde, Otto-Erich
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.01.1993; Elsevier
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Amino Acid Sequence; Biological and medical sciences; Cardiology. Vascular system; Down-Regulation; G-proteins; Heart; Heart - drug effects; Heart Diseases - metabolism; Heart Diseases - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Transplantation; Human cardiac β1-adrenoceptors; human cardica β2-adrenoceptors chronic heart failure; Humans; Medical sciences; Molecular Sequence Data; Myocardial Contraction - drug effects; Receptors, Adrenergic, beta - chemistry; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; β-adrenoceptor desensitization; PET, positron emission tomography; βARK, β-adrenoceptor kinase; PKC, protein kinase C; Human cardiac β 1-adrenoceptors; ACE, angiotensin-converting enzyme; human cardica β 2-adrenoceptors chronic heart failure; G-proteins; β-adrenoceptor desensitization; PKA, protein kinase A; Human; Heart failure; Pathophysiology; Contractility; Cyclic AMP; Cardiovascular disease; Review; Coronary heart disease; Myocardial disease; β-Adrenergic receptor; Vascular disease; Heart rate; Signal transduction; Ischemia; Heart disease; Myocardium
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/0163-7258(93)90030-H

The human heart contains both β 1 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 G i-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.