Recent observations with beta-adrenoceptor blockade. Beneficial effects in hypertension and heart failure.
Carvedilol is a third-generation vasodilating beta-blocker initially approved for the treatment of hypertension. It lowers systemic arterial blood pressure without causing reflex tachycardia and preserves renal function. More recently, carvedilol has been shown to reduce morbidity and mortality in patients with congestive heart failure. This reduction may occur in part via beta-blockade and alpha 1-adrenoceptor blockade, the latter resulting in vasodilation. Importantly, carvedilol and several of its metabolites are potent antioxidants that may inhibit the oxidation of norepinephrine and the subsequent formation of toxic intermediates, such as reactive free radicals in the myocardium. As a result, carvedilol inhibits the expression of certain genes involved in myocardial damage, such as intracellular adhesion molecule-1, free-radical-induced activation of transcription factors, and programmed cell death or apoptosis. In this respect, carvedilol represents a new therapy for the treatment of hypertension and congestive heart failure and combines, in one molecule, a number of potentially beneficial properties.
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Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Feuerstein
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Ohlstein
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D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D011412:Propanolamines / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol