Probucol reduces oxysterol formation in hypertensive rabbits

The role of lipid peroxidation during the pathogenesis of atherosclerosis has been described through numerous studies and has provided compelling evidence for free radical-mediated processes that link hypertension with atherosclerosis. However, there remains only limited information concerning peroxidative processes in hypertension and their modulation by antioxidants. In the present study, the formation of cholesterol oxidation products was used as a measure of in vivo lipid peroxidation after hypertension induced by coarctation of the aorta in New Zealand White rabbits. The rabbits were fed a standard chow diet devoid of cholesterol or cholesterol oxidation products such that the measured cholesterol oxides in the plasma and aortic tissues would most plausibly arise from endogenous oxidation of cholesterol. After 12 weeks of hypertension, all of the measured cholesterol oxides increased significantly over baseline levels in the surgically coarctated animals; however, this increase was significantly less in hypertensive probucol-treated animals. Similarly, the cholesterol oxide content of aortic tissue from the surgically coarctated animals was significantly greater than that found in normotensive control aortas, and probucol treatment significantly reduced the increase in cholesterol oxide content of aortic tissue relative to that of hypertensive animals not receiving the antioxidant. These findings in hypertensive animals suggest that cholesterol oxidation products measured in plasma and aortic tissue can be derived from endogenous free radical activity and that this activity is enhanced under specific pathological conditions.