[An electron microscopic study on the structural alteration of the coronary artery of rats induced by vitamin D3]

Ultrastructural alteration of the coronary artery of the rat induced by a single oral administration of varying doses of vitamin D3 was examined by electron microscopy. Three groups of rats were orally administered 175,000 IU, 350,000 IU and 700,000 IU of vitamin D3/kg body wt. in 1 ml of olive oil, respectively. Another group of rats received 1 ml of olive oil alone as controls. In either group of rats receiving vitamin D3, a significant elevation of serum calcium level was observed at 12, 24 and 48 hours as a maximum level after a single oral administration of vitamin D3, as compared with that of the control group. Ultrastructural changes were first observed mainly in the medial smooth muscle cells of the coronary artery at 24 hours after administration of 700,000 IU of vitamin D3. These were characterized by dissociation of myofilaments, focal necrosis of the cytoplasm and karyolysis. At 48 hours after administration, the coronary arteries of the rats receiving 350,000 IU and 700,000 IU of vitamin D3 showed ultrastructural alteration of medial smooth muscle cells. In the latter group of rats, irregular precipitations of fine, needle-like materials with high electron density were observed in the areas of medial degeneration, and were proved to be calcium salts by X-ray microanalysis. At 72 hours after administration of vitamin D3, such medial structural changes as above were enhanced in the rats receiving both 350,000 IU and 700,000 IU of vitamin D3, but not 175,000 IU. The present study demonstrated that ultrastructural changes of the coronary artery induced by vitamin D3 were, in onset and degree, closely dependent upon the dose of this agent and suggests that the arteriosclerosis induced by vitamin D3 is not initiated by hypercalcemia produced by this agent, but with its direct toxic action to the medial smooth muscle cells.