Pathogenesis of Dietary-Induced Hypercholesteremia in the Rabbit

Abstract

Rabbits on a high cholesterol diet became hypercholesteremic within 24 hours while rats on an identical diet did not in 72 hours. When 0.4 mg/g body weight was administered by stomach tube to both species a similar result followed. Trapping of endogenous cholesterol in the blood by parenteral injection of Triton WR-1339 resulted in a 414% increase in rabbit plasma cholesterol concentration, while a 640% increase took place in rats. Rate of discharge of cholesterol from liver into blood is no greater in the rabbit than in the rat. Balance studies showed rabbits to absorb 76.5% of oral cholesterol while rats absorb only 46%. When absorption in the rat is experimentally increased to that of the rabbit (by addition of bile acid to the diet) or when the absorption of the rabbit is limited to that of the rat by restriction of cholesterol in the diet, the rat still remains normocholesteremic in either case and the rabbit still becomes hypercholesteremic. On a sterol-free diet, rabbits excreted as much sterol/unit body weight as the rats. When rabbits and rats were injected intravenously with rabbits'' hypercholesteremic serum, the rabbits remained hypercholesteremic while the rats quickly regained their pre-injected cholesterol levels. The rabbit proved as capable as the rat of producing plasma lipemia-clearing factor after injection of heparin, and rabbit serum was not resistant to clearing by rat, dog or rabbit clearing factor. Staining for mast cells showed no such cells in the rabbit which were abundant in the rat. Injection of rat serum into rabbits also proved ineffective while injection of rabbit serum into rats did not diminish ability of the rat to remove quickly a cholesterol load from his plasma. Rabbit liver is as capable as that of the rat in metabolic removal of liver tissue cholesterol. The rat liver was capable of storing twice as great a concentration of cholesterol following hypercholesteremia as was the rabbit liver which explains the relative hypercholesteremia of the rabbit. There was a relative inefficiency of the reticulo-endothelial (R-E) cells of the rabbit liver for sections examined by Sudan staining and under polarized light after administration of cholesterol and later of India ink showed much fat and cholesterol in the vicinity of R-E cells in rat liver but very little in rabbit liver. In addition, interference with the R-E cell function of rats by injections of India ink led to appearance of turbidity and hypercholesteremia in those animals, after fat and cholesterol feeding or injection of hypercholesteremic serum. R-E blockage made the rat appear to resemble the rabbit in its cholesterolemia.