Roles of ß-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders.
Handb Exp Pharmacol
; 285: 247-295, 2024.
Article
em En
| MEDLINE
| ID: mdl-38844580
ABSTRACT
ß-Adrenoceptors (ß-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three ß-ARs, ß1-AR, ß2-AR, ß3-AR are localized to the human heart. Activation of ß1-AR and ß2-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of ß1-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of ß1-AR is critical in the pathogenesis of cardiac arrhythmias while activation of ß2-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of ß2-AR in cardiovascular disease, particularly arrhythmia generation. All ß-blockers used therapeutically to treat cardiovascular disease block ß1-AR with variable blockade of ß2-AR depending on relative affinity for ß1-AR vs ß2-AR. Since the introduction of ß-blockers into clinical practice in 1965, ß-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. ß-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. ß-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The ß-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other ß-blockers and is used successfully in the treatment of heart failure. The discovery of ß3-AR in human heart created interest in the role of ß3-AR in heart failure but has not resulted in therapeutics at this stage.
Palavras-chave
Acute coronary syndrome; Anxiety; Arrestin; Arrhythmia; Cardiac ryanodine receptors; Carvedilol; Chronic coronary artery syndrome; Coronary artery disease; Cyclic AMP; Excitation-contraction coupling; Giα-protein; Gsα-protein; Human heart; Human heart failure; Hypertension; Hypertension in pregnancy; Hyperthyroidism; Intrinsic sympathomimetic activity; Migraine; Mirabegron; Phaeochromocytomas and paragangliomas; Phosphodiesterase enzymes; Portal hypertension; Protein kinase A; Ventricular arrhythmias; ß-adrenoceptors; ß-blockers; ß1-adrenoceptor; ß2-adrenoceptor; ß3-adrenoceptor
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta
/
Antagonistas Adrenérgicos beta
/
Insuficiência Cardíaca
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Handb Exp Pharmacol
/
Handb. exp. pharmacol. (Internet)
/
Handbook of experimental pharmacology (Internet)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália