Two patterns of lipid deposition in the cholesterol-fed rabbit

A central feature of arterial lipid deposition is its nonuniform and variab le distribution. In immature human and rabbit aortas, spontaneous lesions o ccur most frequently downstream of branch points, but they tend to occur up stream of the same branches at later ages. In cholesterol-fed rabbits, the juvenile pattern has been seen regardless of age. These distributions may b e determined by transport properties of the arterial wall, because uptake o f plasma macromolecules is elevated downstream of aortic branches in immatu re rabbits and upstream in mature ones, except during cholesterol feeding, when the juvenile pattern is seen in adult vessels. The effect of cholester ol could reflect its inhibitory influence on the nitric oxide (NO) pathway because the adult transport pattern is NO dependent. Using protocols expect ed to preserve NO function and the mature pattern of transport during hyper cholesterolemia, we made 2 attempts to induce upstream disease in rabbits. In trial I, plasma concentrations of cholesterol were kept within the norma l human range for 15 weeks by using dietary levels of 0.05% to 0.2%. Althou gh disease patterns reverse with age in human vessels exposed to these conc entrations, lesions in both immature and mature rabbits occurred downstream of intercostal branch ostia. Trial II used older rabbits, a different base diet containing more vitamin E (96 mg/kg rather than 57 mg/kg), and higher levels of cholesterol (1%, administered for 8 weeks). For some animals, ex tra vitamin E (2000 mg/kg) was added to the diet. The mature pattern of lip id deposition was apparent around intercostal branches in the first group a nd was accentuated by the additional vitamin E, a change that was associate d with a significant increase in the plasma concentration of NO metabolites . Spontaneous lesions, assessed on the base diet, were too rare to have inf luenced these distributions. This is the first report of upstream disease i n the cholesterol-fed rabbit. The results support but do not prove the view that NO and transport are important in atherogenesis.