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Published on: June 11, 2020
The roles of alpha- and beta-adrenoceptor stimulation in myocardial ischaemia
1Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Insights
Beta-adrenoceptor (AR) stimulation before or during heart ischemia offers protective effects. Understanding these adrenoceptor subtype actions is crucial for developing new cardiovascular therapies.
Area of Science:
- Cardiovascular Pharmacology
- Cellular Cardiology
Background:
- Beta-adrenoceptor (AR) ligands are vital in cardiovascular medicine.
- Myocardial ischemia and reperfusion cause significant cardiac damage.
- Adrenoceptor stimulation effects vary based on timing and subtype.
Purpose of the Study:
- To review the effects of beta-AR subtype stimulation on the heart during ischemia and reperfusion.
- To explore the role of endogenous catecholamines and adrenoceptor subtypes in preconditioning.
- To assess the clinical significance of AR activation in myocardial ischemia.
Main Methods:
- Literature review of adrenoceptor (AR) stimulation in myocardial ischemia.
- Analysis of effects of beta(1)-, beta(2)-, and beta(3)-AR activation before, during, and after ischemia.
- Examination of transduction pathways and apoptosis.
Main Results:
- Beta-AR stimulation can be protective (preconditioning) or detrimental depending on application timing.
- Endogenous catecholamines and specific AR subtypes mediate these effects.
- AR activation influences apoptosis and signal transduction pathways.
Conclusions:
- Adrenoceptor stimulation has complex, context-dependent effects on myocardial ischemia-reperfusion injury.
- Understanding these mechanisms is key for optimizing beta-AR antagonist therapy.
- Further research may reveal novel therapeutic strategies for heart protection.
Abstract:
beta-Adrenoceptor (AR) ligands have been the mainstay of cardiovascular therapy for decades, with beta-AR antagonist being used for hypertension, angina and myocardial infarction and adrenaline in use for cardiopulmonary resuscitation for nearly 100 years. Ischaemia of the heart through coronary artery occlusion causes cell injury and death through necrosis and apoptosis. Reperfusion of the ischaemic myocardium results in cardiac dysfunction and infarction. Stimulation of alpha- and beta-ARs in the ischaemic heart have variable and inconsistent effects depending on when the agonist is applied. This review describes the different effects of stimulation of the three established beta-AR subtypes (beta(1)-, beta(2)- and beta(3)-ARs) either before ischaemia (preconditioning) or during ischaemia and reperfusion of the heart (postconditioning). Brief periods of ischaemia preceding a major ischaemic episode can have a protective effect against post-ischaemia-reperfusion damage, known as ischaemic preconditioning. This review considers the role of endogenous catecholamines released during preconditioning and the nature of the adrenoceptor subtypes that mediate these effects. The clinical significance of this to the use of beta-AR antagonists is considered. The transduction pathways and effects on apoptosis of the cardioprotective and deleterious effects of AR activation are considered. This commentary reviews the literature and attempts to bring together a unified synopsis of the effects of adrenoceptor stimulation in myocardial ischaemia and the potential clinical relevance.
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