VASCULAR CALCIUM OVERLOAD PRODUCED BY VITAMIN-D-3, IN RATS - EFFECT OF TREATMENT WITH SR-33805, A NOVEL CALCIUM-ENTRY BLOCKER

The effect of SR 33805, a novel calcium entry blocker, on calcium over load was studied in six vascular beds in rat. Fantofarone, a parent co mpound, and verapamil were used as reference calcium entry blockers. C alcium overload induced with a single dose (300 000 IU, i.m. of vitami n D-3) was measured by means of atomic absorption and histological tec hniques. From the time-course of calcium overload, a treatment period of 3 days was selected to determine the effects of drug treatment. The compounds were given orally twice a day in the following dose ranges: SR 33805 2-100 mg/kg, fantofarone 10-300 mg/kg, verapamil 100 mg/kg. SR 33805 significantly decreased the calcium content beginning at the dose of 2 mg/kg in the thoracic aorta, 5 mg/kg in the mesenteric arter y and 30 mg/kg in the heart, Fantofarone and verapamil had the same ef fect at the dose of 100 mg/kg. Histological assessment of the heart re vealed that lesions appearing in the tissue adjacent to the arteries w ere significantly diminished by treatment with SR 33805 at a dose whic h produced a significant decrease in the arterial calcium content. Thu s, SR 33805 can inhibit both calcium overload and its deleterious cons equences and its actions are evident at doses as low as 2 mg/kg.