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The influence of estradiol on deposition of cholesterol in tissues of ovariectomized rats on normal and high lipid diets was studied. Concomitantly the influence of a contraceptive steroid combination was studied in a similar manner in intact rats. It was found that the high lipid diet resulted in increased deposition of cholesterol in aorta, heart, liver and kidney. The presence of either endogenous or exogenous hormones accentuated the deposition of cholesterol in the kidney and resulted in significantly higher systolic blood pressures in these rats. In the rats on a high lipid diet, the concentration of cholesterol in the kidney correlated positively with systolic blood pressure. It is concluded that estrogen and high lipid diet exert a synergistic effect on deposition of cholesterol in kidney. The positive correlation between kidney cholesterol concentration and systolic blood pressure suggests a possible role for kidney lipid deposition in the hypertensive effect of estrogens.

The effects of sex hormones on atherosclerosis and collagen synthesis in blood vessels were studied in rabbits fed an atherogenic diet. Ovariectomy without hormone replacement resulted in significantly greater degree of atherosclerosis and collagen synthesis in the aortic arch when compared with the intact state. The administration of estradiol to ovariectomized rabbits resulted in a degree of atherosclerosis and collagen synthesis similar to that of intact rabbits. Ovariectomized rabbits administered progesterone on the other hand resembled the ovariectomized rabbits without hormone replacement. Specific activity of hydroxyproline in individual specimens of the arch correlated strongly with degree of atherosclerosis. An analysis of regional variation demonstrated declining values for collagen synthesis in the caudal direction along the aorta. Collagen synthesis was much higher in the portal vein as compared with the inferior vena cava. Plasma cholesterol values were higher in the ovariectomized rabbits than in the intact rabbits. Tissue deposition of cholesterol paralleled the degree of atherosclerosis.

The administration of estradiol to both castrated and noncastrated male rats was associated with significantly increased plasma cholesterol levels as compared to controls, the estradiol in the noncastrated rats overriding the tendency of testosterone to lower plasma cholesterol.

Aortic collagen and elastin were quantitated in three groups of castrated and two groups of noncastrated male rats treated by intramuscular injection for 3 wk with oil, testosterone, or estradiol. The greatest differences were found between the castrated rats receiving testosterone and those receiving estradiol, the estradiol-treated rats having significantly lower total collagen, percent collagen, total elastin, and collagen/elastin (C/E), and higher percent elastin than those rats receiving testosterone. In noncastrated rats, administration of estradiol resulted in significantly lower total collagen, percent collagen, total elastin, and C/E. Systolic blood pressure was highest in rats receiving testerone and lowest in rats receiving estradiol. It is concluded that 1) estradiol in the presence or absence of testosterone decreases total accumulation of vascular connective tissue and alters the proportions of collagen and elastin so that the vessel is more distensible, 2) testosterone has an opposite but less marked effect than estradiol on vascular connective tissue, and 3) estradiol and testosterone alter blood pressure in opposite directions in the male rat.