Progressive microcirculatory changes caused by hypercholesterolemia in rats.

The progressive microcirculatory changes caused by hypercholesterolemia were studied in the rat cremaster model by use of intravital microscopy. Male Sprague-Dawley rats were fed either a normal chow diet or a chow diet supplemented with 1% cholesterol and 0.5% cholic acid for 1, 3, or 5 wk before experimentation. After 3 wk on the diet, hypercholesterolemia produced a significantly decreased vasoconstrictor response to norepinephrine in both arterioles and venules. After 5 wk, there was also significantly reduced macromolecular leakage induced by exogenous histamine and compound 48/80 in the high-cholesterol group. However, there was no change in the degree of base-line macromolecular leakage. Platelet thrombi formation induced by light activation of intravascular fluorescein isothiocyanate tagged to bovine serum albumin was slightly increased by hypercholesterolemia. Despite these microcirculatory changes there was no microscopic evidence of atheromatous pathology after 5 wk on the cholesterol diet. These results suggest a progressive nonspecific receptor desensitization and decreased inflammatory response shortly after the initiation of elevated serum cholesterol but before any histological evidence of atherosclerosis.