Probucol reduces oxysterol formation in hypertensive rabbits

The role of lipid peroxidation during the pathogenesis of atherosclerosis h as been described through numerous studies and has provided compelling evid ence for free radical-mediated processes that link hypertension with athero sclerosis. However, there remains only limited information concerning perox idative 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 c oarctation of the aorta in New Zealand White rabbits. The rabbits were fed a standard chow diet devoid of cholesterol or cholesterol oxidation product s such that the measured cholesterol oxides in the plasma and aortic tissue s would most plausibly arise from endogenous oxidation of cholesterol. Afte r 12 weeks of hypertension, all of the measured cholesterol oxides increase d significantly over baseline levels in the surgically coarctated animals; however, this increase was significantly less in hypertensive probucol-trea ted animals. Similarly, the cholesterol oxide content of aortic tissue from the surgically coarctated animals was significantly greater than that foun d in normotensive control aortas, and probucol treatment significantly redu ced 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 measure d in plasma and aortic tissue can be derived from endogenous free radical a ctivity and that this activity is enhanced under specific pathological cond itions.