The effect of feeding a diet supplemented with
lipids and containing 2%
cholesterol on the endothelium-dependent relaxation of rabbit aorta to
acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2%
cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2%
cholesterol diet or a standard rabbit diet. The animals were anesthetized with
pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2%
cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of
atherosclerosis in the aorta was assessed by
Sudan Red staining, estimation of tissue
cholesterol, and light and electron microscopy. The relaxation response to
acetylcholine was measured in rings of the thoracic aorta following precontraction with
norepinephrine (-6.0 log mol/l). The relaxation was significantly impaired in aortas from rabbits fed the 2%
cholesterol diet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2%
cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2%
cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.