Strain-dependent differences in the pattern of aortic lipid deposition in cholesterol-fed rabbits

Spontaneous lesions develop downstream of branch points in immature human and rabbit aortas, but occur more frequently at the sides and upstream of these sites in mature vessels. Cholesterol-induced lesions in mature rabbits, however, have shown the downstream distribution in one trial and the more upstream distribution in another. We tested the hypothesis that this discrepancy reflected a difference in the degree of impairment of the nitric oxide pathway. Mature rabbits were fed cholesterol-enhanced versions of the two base diets used in the previous trials, and some were given additional vitamin E or l-arginine to protect the NO pathway or L-NAME to inhibit it. Unexpectedly, the rabbits developed a lesion pattern intermediate between the two previously described, and this distribution was unaffected by the base diet or supplements. Consequently, an exploratory study was conducted to investigate possible effects of other differences between the two earlier trials. These were the precise age of the mature rabbits and the feeding protocol employed; both base diets again were used. Two different lesion patterns were observed in this trial, but there was no systematic effect of any of the controlled variables. Instead, there appeared to be an influence of the supplier from which the rabbits had been obtained. A multivariate analysis of all four trials confirmed that the pattern of disease was associated with rabbit strain, and not with base diet, cholesterol level, or precise age.