CARVEDILOL, A NEW ANTIHYPERTENSIVE, PREVENTS OXIDATION OF HUMAN LOW-DENSITY-LIPOPROTEIN BY MACROPHAGES AND COPPER

Growing evidence indicates that oxidized low-density lipoprotein (LDL) may promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. Carvedilol is a vasodilating, beta-adrenoceptor blocking agent. As a new antihypertensive drug, carvedilol is unique by virtue of its potent antioxidant activity. Therefore, we tested the ability of carvedilol to inhibit the oxidation of LDL by either macrophages or Cu2+. Carvedilol inhibited LDL oxidation by macrophages in a dose with an IC50 value of 3.8 muM, as assessed by a thiobarbituric acid reactive substance (TBARS) assay. Under the same conditions, propranolol showed only a mild inhibitory effect (IC50 > 100 muM), while pindolol, atenolol and labetalol had almost no effect. Carvedilol, at 10 muM, almost completely inhibited the macrophage-induced increase in electrophoretic mobility of LDL, while other beta-blockers at 50-300 muM had no significant effect. Carvedilol inhibited superoxide release from mouse macrophages, which correlated well with its inhibition of LDL oxidation. Carvedilol also inhibited Cu2+-induced LDL oxidation with an IC50 value of 17 muM, while all other beta-blockers were inactive up to 300 muM. These observations suggest that carvedilol might not only be an effective antihypertensive drug, but might also be effective in prevention of atherosclerosis.