vitamin-d-2 and nilvadipine

Nilvadipine and other calcium antagonists were studied for their effect on 1-alpha-hydroxyvitamin D3 (1 - alpha (OH)D3)-induced aortic calcium deposition in rats. The animals were treated orally with 1-alpha (OH)D3 (10 micrograms/kg) for 2 weeks. Calcium antagonists were given orally twice a day during the same period. The aortic calcium content in 1-alpha (OH)D3-treated rats increased to about 100 times that in the control. Nilvadipine reduced the aortic calcium deposition dose-dependently, with percent inhibition of 6, 43, 72 and 92%, at doses of 0.1, 1, 10 and 100 mg/kg, respectively. Similar activities were obtained for the other calcium antagonists except diltiazem which had no effect even at the largest dose of 100 mg/kg. According to the ED50 values, nilvadipine (2.2 mg/kg) was more potent than nifedipine (23.2 mg/kg), nicardipine (12.4 mg/kg) and verapamil (32.0 mg/kg). Scanning and transmission electron microscopy showed clear-cut degenerative changes in the endothelial cells after 1-alpha (OH)D3 treatment. Nilvadipine exerted a protective effect against these degenerative changes but not against 1-alpha (OH)D3-induced hypercalcemia. Furthermore, the drug had only minimal effect on in vitro calcification of the aorta. Our findings suggest that nilvadipine inhibits aortic calcification by protecting the aortic wall cells.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Calcium; Calcium Channel Blockers; Dose-Response Relationship, Drug; Ergocalciferols; In Vitro Techniques; Male; Microscopy, Electron, Scanning; Nifedipine; Rats; Rats, Inbred F344