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  • Title: Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection.
    Author: Feuerstein GZ, Ruffolo RR.
    Journal: Eur Heart J; 1995 Jul; 16 Suppl F():38-42. PubMed ID: 8521883.
    Abstract:
    Carvedilol is a vasodilating, beta-adrenoceptor antagonist currently marketed for the treatment of mild to moderate hypertension. Carvedilol acts to reduce total peripheral resistance by blocking peripheral vascular alpha 1-adrenoceptors, thereby producing systemic arterial vasodilation, while at the same time inhibiting reflex tachycardia through the blockade of myocardial beta-adrenoceptors. In addition to its established efficacy and safety as an antihypertensive agent, carvedilol has been shown to produce significant cardioprotection in experimental animal models of acute myocardial infarction, with the most dramatic effect being observed in the pig model of myocardial ischaemia and reperfusion, where the reduction in infarct size reached 91%. Recent pharmacological studies have revealed additional novel properties of carvedilol which may account for the marked protection produced by the drug in the ischaemic myocardium and which may also result in protection against other chronic pathological processes, such as atherosclerosis and acute vascular injuries. The latter arise from surgical procedures, such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. Specifically, carvedilol, as well as some of its hydroxylated metabolites, are potent antioxidants. In physicochemical, biochemical and cellular assays, carvedilol and several of its metabolites prevent lipid peroxidation and the depletion of endogenous antioxidants, such as vitamin E and glutathione. Moreover, carvedilol and its metabolites prevent the oxidation of LDL to oxidized LDL, the latter being directly cytotoxic and known to activate monocytes/macrophages and to stimulate foam cell formation. In addition, carvedilol was found to inhibit both rat and human vascular smooth muscle cell proliferation and migration.(ABSTRACT TRUNCATED AT 250 WORDS)
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