Cardiac adrenoceptors in the failing heart: effect of intervention.
The sympathetic nervous system is chronically activated in heart failure. This results in a reduction in numbers and sensitivity of beta-receptors, making the heart less responsive to the actions of catecholamines. This is specific to beta-receptors, the adenycyclase system being largely unaffected. Sympathomimetic agents are still used in patients with heart failure to augment cardiac contractility, but tachyphylaxis limits their long-term usefulness, and they may actually cause further myocardial damage. On the other hand, beta-blockade can improve sensitivity to catecholamines and cardiac action in some patients with severe left ventricular dysfunction, although this treatment can be hazardous and cannot yet be routinely recommended. Partial beta-agonists are theoretically useful since they can provide baseline sympathetic drive while protecting the heart against excessive sympathetic stimulation and down-regulation of beta-receptors. Xamoterol, a partial agonist with half the sympathetic activity of isoprenaline, has been shown to be superior to placebo and to digoxin in patients with mild to moderate heart failure.
Fowler
M B
MB
Cardiology Division, Stanford University Medical Center, California 95405.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta