Novel mechanisms in the treatment of heart failure: inhibition of oxygen radicals and apoptosis by carvedilol.
Carvedilol is a novel cardiovascular drug of proven efficacy in the treatment of hypertension, angina, and heart failure. Several mechanisms may account for the beneficial effects of carvedilol in patients with heart failure. As with other beta-blockers, blockade of cardiac beta-adrenergic receptors (both beta1 and beta2), and hence reduction of cardiac work load and oxygen consumption, plays an important role in the actions of this agent. Additional benefit is provided by vasodilation (alphal-adrenergic blockage) at peripheral resistance vessels, which decreases preload and after-load, thereby further reducing cardiac work and wall tensions. In addition, potential advantages of carvedilol resulting from alpha1-adrenergic blockade are likely because alpha1-adrenergic receptors mediate cardiac remodeling by inducing hypertrophy. Finally, carvedilol is a potent antioxidant and is unique among beta-blockers in this respect. In recent years, evidence has accumulated in support of the role played by reactive oxygen radicals in chronic pathological states of the myocardium. In this article, the role of oxygen radicals in heart failure is discussed with special reference to apoptosis, a phenomenon believed to be involved in progressive cardiac myocyte loss in ischemic or myopathic heart diseases. The potential role of the antioxidant actions of carvedilol, especially in prevention of apoptotic cell death, is highlighted as a novel mechanism of action in heart failure.
Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA.
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Feuerstein
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Yue
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Ruffolo
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D011412:Propanolamines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D016166:Free Radical Scavengers; D005609:Free Radicals; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol