Inhibition of vitamin D3-induced vascular calcification by carbocromen

High doses of vitamin D3 induce myocardial lesions, necrotic alterations, and calcification of the vascular smooth muscle, (Mönckeberg arteriosclerosis) (6). These effects are accompanied by an increased calcium influx into the wall of the aorta and mesenterial vessels (1). Prophylactic application of MgCl2 nearly prevents this calcium overload, whereas KCl or calcium antagonists are less active. In our studies, the uptake of calcium-45 4 days after a single dose of vitamin D3 (90,000 IU/200 g) was increased in rat heart and aorta by a factor of 3 to 7, and up to 30-fold in mesenterial vessels. Application of carbocromen (10 mg/kg b.i.d.) for 4 days decreases the vitamin D3-induced radiocalcium uptake by 44 (aorta) to 67% (mesenterial vein), MgCl2 (15 mmol/kg b.i.d.) by 46 (mesenterial vein) to 92% (mesenterial artery), and verapamil (5 mg/kg b.i.d.) by 15 (aorta) to 44% (mesenterial vein).