AORTIC PERMEABILITY TO LDL DURING ESTROGEN THERAPY - A STUDY IN NORMOCHOLESTEROLEMIC RABBITS

17 beta-Estradiol has recently been found to inhibit atherogenesis by mechanisms that are in part independent of the estrogenic action on pl asma lipoprotein levels. Since aortic permeability to low-density lipo protein (LDL) in normocholesterolemic rabbits is a strong predictor fo r subsequent atherosclerosis during hypercholesterolemia, the present study investigated a possible influence of 17 beta-estradiol on aortic permeability to LDL. Twenty rabbits were initially ovariectomized and then fed a nonatherogenic diet for 10 weeks. One group of rabbits (n= 10) received 4 mg of 17 beta-estradiol orally per day; the other group (n=10) received placebo. Serum concentrations of very-low-density lip oprotein cholesterol and triglycerides increased significantly more in the placebo group than in the estrogen group (P<.03), whereas there w ere no statistically significant differences between groups in LDL, hi gh-density lipoprotein, or total cholesterol. At the end of the experi ment, I-125-LDL was injected intravenously into each rabbit. Aortas we re removed 3 hours later, and the aortic permeability to LDL was calcu lated from the radioactivity in the plasma and the aortic intima/inner media. The aortic permeability to LDL was virtually identical in the 17 beta-estradiol (31.6+/-7.2 nL.cm(-2).h(-1)) and the placebo (36.9+/ -7.9 nL.cm(-2).h(-1)) groups (mean+/-SEM). The aortic cholesterol cont ent was also similar in the two groups. These data suggest that the pl asma lipid-independent antiatherogenic effect of estradiol is not medi ated through an effect on aortic permeability to LDL but rather is rel ated to the metabolism of the lipoproteins after they have entered the arterial wall.