Beta- and alpha-adrenoceptor-agonists and -antagonists in chronic heart failure.
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.
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Zentrum für Innere Medizin, Abteilung für Nieren- und Hochdruckkrankheiten, Universitätsklinikum, Essen, FRG.
D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013565:Sympatholytics / Q000627:therapeutic use*; D013566:Sympathomimetics / Q000627:therapeutic use*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics; D013566:Sympathomimetics