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Beta- and alpha-adrenoceptor-agonists and -antagonists in chronic heart failure
1Zentrum für Innere Medizin, Abteilung für Nieren- und Hochdruckkrankheiten, Universitätsklinikum, Essen, FRG.
Insights
Beta-blockers may benefit chronic heart failure patients by restoring cardiac beta-adrenoceptor function and protecting the heart. Beta-agonists offer limited value due to potential receptor down-regulation.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Cardiac beta-adrenoceptor function is diminished in chronic heart failure, correlating with disease severity.
- Beta-adrenoceptor agonists may be ineffective or detrimental by further down-regulating receptors.
- Alpha-adrenoceptors have limited therapeutic relevance in heart failure due to low numbers and lack of selective agonists.
Purpose of the Study:
- To evaluate the therapeutic potential of modulating cardiac adrenoceptors in chronic heart failure and acute myocardial ischemia.
- To assess the role of beta-adrenoceptor agonists versus antagonists in heart failure.
- To explore the implications of alpha-adrenoceptor function in cardiac conditions.
Main Methods:
- Review of existing literature on adrenoceptor function in heart failure and ischemia.
- Analysis of the effects of agonists and antagonists on cardiac beta-adrenoceptors.
- Consideration of adrenoceptor subtypes and their clinical implications.
Main Results:
- Beta-adrenoceptor antagonists show promise in chronic heart failure by protecting the myocardium and restoring receptor function.
- In acute myocardial ischemia, beta-adrenoceptor agonists may lack clinical value due to increased receptor sensitivity.
- Beta-adrenoceptor antagonists may be beneficial in acute ischemia by blocking excessive catecholamine activation.
Conclusions:
- Beta-adrenoceptor antagonists are potentially beneficial in both chronic heart failure and acute myocardial ischemia.
- The use of beta-adrenoceptor agonists is likely limited in these cardiac conditions.
- Modulating cardiac adrenoceptors offers a potential therapeutic strategy for heart failure and ischemia.
Abstract:
In patients with chronic heart failure, cardiac beta-adrenoceptor function is decreased, and this decrease is related to the degree of heart failure. Under these conditions, treatment with beta-adrenoceptor agonists seems to be of limited value as it might further down-regulate cardiac beta-adrenoceptors, resulting, finally, in a loss of therapeutic efficacy. However, beta-adrenoceptor antagonists might have beneficial effects, because they can protect the myocardium from the deleterious effects of elevated endogenous catecholamines and can, simultaneously, restore the previously down-regulated beta-adrenoceptor function. Stimulation of cardiac alpha-adrenoceptors, however, seems not to be of any therapeutic value in patients with chronic heart failure, because a) the number of alpha-adrenoceptors in the human heart is very low and its function is not completely understood, and b) no alpha-adrenoceptor agonist is presently available that selectively stimulates cardiac alpha-adrenoceptors without concomitantly activating vascular alpha-adrenoceptors. In acute myocardial ischemia, cardiac beta-adrenoceptors increase; this increase is--at least in early acute myocardial ischemia--accompanied by an increased beta-adrenoceptor functional responsiveness; thus, under these conditions, beta-adrenoceptor agonists again might not be of clinical value, while beta-adrenoceptor antagonists may exert beneficial effects, because they can block (over)activation of the sensitized beta-adrenoceptors by elevated endogenous catecholamines.