Correction of enhanced endothelial permeability by cessation of cholesterol feeding.

Changes in endothelial permeability and the transport of macromolecules may be important in the initiation and/or progression of atherosclerosis. We have previously shown, with a carotid artery preparation isolated in situ with intact adventitia, that long-term cholesterol feeding in rabbits will result in a seven- to tenfold increase in 125I albumin transport across the artery into the systemic circulation. The current studies were undertaken to determine whether this abnormality of enhanced permeability could be reversed by cessation of cholesterol feeding and correction of the hyperlipidemia. Two groups of rabbits were fed either a standard Rabbit Chow or a diet containing 1.5% cholesterol and 5.2% corn oil for 12 to 15 weeks. Another group of rabbits was given cholesterol for 12 to 15 weeks with change to standard rabbit chow for an additional 22 to 24 weeks after which albumin transport studies were then performed. Mean plasma cholesterol level after 12 to 15 weeks of cholesterol feeding was 2052 +/- 395 mg/dl. After the animals were withdrawn from the cholesterol diet for 22 to 24 weeks, the mean plasma cholesterol level decreased to 80 +/- 21 mg/dl. The mean plasma cholesterol value in chow-fed animals was 39 +/- 6 mg/dl. Perfusion studies were done with 125I-labeled albumin and plasma radioactivity served as a measure of transport across the carotid artery. The average level of albumin transport across the artery into venous blood in the cholesterol-fed animals (13,911 dpm/ml of plasma) was significantly greater than that of control animals (2049 dpm/ml of plasma).(ABSTRACT TRUNCATED AT 250 WORDS)