This study was to examine the effects of estrogen replacement on atherosclerosis formation in ovariectomized cholesterol-fed rabbits. We also examined serum levels of nitrite/nitrate, stable metabolites of nitric oxide, to investigate the involvement of nitric oxide. Female New Zealand White rabbits were ovariectomized and divided into 3 groups; 1) fed a normal diet (ND group, n=5), 2) fed a 1% cholesterol diet (CD group, n=6), or 3) fed a 1% cholesterol diet and received estrogen replacement (CD + E group, n=7). After 3 months, the rabbits were sacrificed to examine atherosclerosis formation. Atherosclerosis was not observed in ND. The oil red O-positive area in the aorta was significantly greater in CD than in CD + E (CD, 17.3±2.2; CD+E, 9.3±0.8%, p<0.05). Stenosis of the coronary artery was also significantly greater in CD than in CD+E (CD, 30.6±9.7; CD+E, 6.7±2.9%, p<0.05). There was no significant difference in serum lipids between CD and CD+E. Serum nitrite/ nitrate levels were significantly lower in CD than in ND (ND, 37.6±3.6 ; CD, 25.3±3.1μM, p<0.05). There was a non-significant trend towards higher nitrite/nitrate levels after estrogen replacement (CD+E, 34.4±3.8μM, p=0.08vs.CD). These results suggest that direct actions on vascular wall including nitric oxide production contribute to the antiatherogenic effects of estrogen. J Atheroscler Thromb, 1996 ; 3 : 114-119.
Japan Atherosclerosis Society