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

Abstract

The protective effects of carvedilol, a new β-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 β-blockers. Carvedilol dose-dependently inhibited oxygen radical-induced lipid peroxidation (50% inhibition at 2.6 μmol/L) and glutathione depletion (50% inhibition at 1.8 μmol/L) in the cells. Under the same conditions, other β-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 μmol/L and increased the cell survival in a dose-dependent manner, whereas other β-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.