The roles of alpha- and beta-adrenoceptor stimulation in myocardial ischaemia.
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.
Broadley
K J
KJ
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Penson
P E
PE
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D016887:Cardiopulmonary Resuscitation; D002395:Catecholamines / Q000494:pharmacology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002395:Catecholamines