Aortic prolyl hydroxylase and the development of arteriosclerosis in the female breeder rat.

Female breeder rats develop arteriosclerosis spontaneously. The primary lesions seen in the early stages of the disease consist of subintimal and adjacent medial ground substance accumulations. With repeated breeding there is extensive elastolysis and calcification in the aorta. In aortae with developing arterial disease, prolyl hydroxylase activity is elevated as is both aortic protein and hydroxyproline, indicative of increased collagen deposition associated with the sclerotic degeneration. As the disease becomes very severe, however, prolyl hydroxylase activity declines, possibly associated with decreased metabolic activity in the severely calcified aorta. Lactation, followed by forced weaning, may condition the development or arterial disease through effect on collagen metabolism. During the first breeding cycle, aortic prolyl hydroxylase activity is elevated for 5 to 10 days after weaning. This increased collagen metabolism in the aorta may be a primary event in the development of the advanced calcific lesions characteristic of the lesions in breeder rats, and may be affected by hormones associated with different phases of the reproductive cycle.