Vascular calcium overload produced by vitamin D3, in rats. Effect of treatment with SR 33805, a novel calcium entry blocker

Abstract

The effect of SR 33805, a novel calcium entry blocker, on calcium overload was studied in six vascular beds in rat. Fantofarone, a parent compound, and verapamil were used as reference calcium entry blockers. Calcium overload induced with a single dose (300,000 IU, i.m. of vitamin D3) was measured by means of atomic absorption and histological techniques. 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 artery and 30 mg/kg in the heart. Fantofarone and verapamil had the same effect at the dose of 100 mg/kg. Histological assessment of the heart revealed that lesions appearing in the tissue adjacent to the arteries were significantly diminished by treatment with SR 33805 at a dose which produced a significant decrease in the arterial calcium content. Thus, SR 33805 can inhibit both calcium overload and its deleterious consequences and its actions are evident at doses as low as 2 mg/kg.

Biochemical and Pharmacological Properties of SR 33805, a Novel Ca2+ Channel Antagonist

“…This treatment produces large increases in arterial Ca2+ content (19,22) and impairment of mitochondria1 and contractile functions. The effects of SR 33805 on Ca2+ overload produced by vitamin D, has been studied in various vascular beds (coronary, mesenteric, femoral, and carotid arteries, thoracic and abdominal aorta) by assessing total Ca2 + content (using atomic absorption spectroscopy) and histological analysis (using von Kossa's dye) (13).…”