Carvedilol, a new beta-adrenoceptor antagonist and vasodilator antihypertensive drug, inhibits superoxide release from human neutrophils.
Carvedilol produced a dose-dependent inhibition of superoxide (O2-) release from human neutrophils (PMNs) (IC50 = 28 microM) and scavenged O2- generated during dihydroxyfumaric acid (DHF) autooxidation (IC50 = 41 microM). Other beta-blockers, such as celiprolol, labetalol and atenolol, or the antioxidant, 'lazaroid', U74500A had no effect on O2- either released from PMNs or generated during DHF autooxidation. Propranolol, at 0.3 mM, inhibited O2- release from PMNs (73%) but failed to scavenge O2- generated from DHF. The novel free radical-scavenging effect of carvedilol may contribute to the cardioprotective activity of the compound.
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
T L
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Yue
P J
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McKenna
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Ruffolo
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Feuerstein
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D016166:Free Radical Scavengers; D005650:Fumarates / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D016166:Free Radical Scavengers; D005650:Fumarates; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D013481:Superoxides; C005998:dihydroxyfumarate; D013755:Tetradecanoylphorbol Acetate