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Hypertension, Vol 22, 922-928, Copyright © 1993 by American Heart Association

ARTICLES

Carvedilol, a new antihypertensive agent, prevents lipid peroxidation and oxidative injury to endothelial cells

TL Yue, PJ Mckenna, JL Gu, HY Cheng, RR Ruffolo Jr and GZ Feuerstein
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

The protective effects of carvedilol, a new beta-adrenergic receptor blocker and vasodilating antihypertensive agent, against oxygen free radical-mediated injury were studied in cultured bovine endothelial cells and compared with five other beta-blockers. Carvedilol dose- dependently inhibited oxygen radical-induced lipid peroxidation (50% inhibition at 2.6 mumol/L) and glutathione depletion (50% inhibition at 1.8 mumol/L) in the cells. Under the same conditions, other beta- blockers--propranolol, labetalol, pindolol, atenolol, and celiprolol-- had only mild or no effect. Moreover, carvedilol protected against oxygen radical--mediated cell damage, as assessed by cellular lactate dehydrogenase release, with a 50% inhibition at 4.1 mumol/L and increased the cell survival in a dose-dependent manner, whereas other beta-blockers had mild or no effects. Pretreatment of the cells with carvedilol for 7 days significantly enhanced the protective effects of carvedilol. Using 2-methyl-2-nitrosopropane as a trapping agent, the spin adduct in cell lipids was monitored by electron paramagnetic resonance. Carvedilol dose-dependently decreased the intensity of the free radical signals, indicating its free radical-scavenging ability. The prevention of oxidative injury to endothelial cells might potentially contribute to the clinical beneficial effects of carvedilol as an antihypertensive agent.

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