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Cardiovascular Research 1995 30(6):1038-1043; doi:10.1016/S0008-6363(95)00186-7
© 1995 by European Society of Cardiology
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Copyright © 1995, European Society of Cardiology

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

P. Chatelaina,*, J. Moutonb, G. Feysb, A. Laruelb and A.S. Manningb

aSanofi Recherche 371, rue du Professeur J. Blayac, 34184 Montpellier Cédex 04, France
bSanofi Pharma Research Center, Avenue de Béjar, 1 B-1120 Brussels, Belgium

* Corresponding author.

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.

KEYWORDS SR 33805; Arterial tone; Vitamin D3; Calcium antagonist; Rat arteries


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