Protective effects of carvedilol in the myocardium.
Beta blockers have long been used in the treatment of systemic hypertension, where they effectively lower blood pressure and, in so doing, they decrease left ventricular hypertrophy. The sympathetic nervous system is activated in patients with congestive heart failure, and therefore it is logical that beta blockers may also provide benefit in these patients. As such, beta blockers are currently being evaluated in several large clinical trials in congestive heart failure. One particular drug, carvedilol, is a third-generation vasodilating beta blocker that is marketed for the treatment of hypertension. The drug lowers systemic arterial blood pressure without producing reflex tachycardia and preserves renal function. Carvedilol decreases mortality by 65% and decreases hospitalization by 29% in patients with congestive heart failure. The effects of carvedilol in heart failure may result, at least in part, from beta blockade as well as vasodilation, the latter resulting from alpha(1)-adrenoceptor blockade. Interestingly, carvedilol has a number of additional properties that may also provide benefit in these patients. Carvedilol and several of its metabolites are potent antioxidants that may inhibit catecholamine toxicity resulting from the oxidation of norepinephrine and the subsequent formation of toxic intermediates, including the generation of reactive oxygen free radicals in the myocardium. As a result of its antioxidant activity, carvedilol also blocks the expression of several genes involved in myocardial damage and cardiac remodeling, and the drug inhibits free radical-induced activation of transcription factors and programmed cell death (apoptosis). Carvedilol is a novel beta blocker that is highly effective in the treatment of hypertension and congestive heart failure, and combines in one molecule a number of important pharmacologic properties.
Feuerstein
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Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Bril
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Ruffolo
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002227:Carbazoles; D016166:Free Radical Scavengers; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol