Vascular calcium overload produced by vitamin D3, 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 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.
Chatelain
P
P
Sanofi Recherche 371, Montpellier, France.
Mouton
J
J
Feys
G
G
Laruel
A
A
Manning
A S
AS
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000378:metabolism; D002114:Calcinosis / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013450:Sulfones / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007211:Indoles; D007212:Indolizines; D010627:Phenethylamines; D013450:Sulfones; C084255:SR 33805; D002762:Cholecalciferol; D014700:Verapamil; C059901:fantofarone; D002118:Calcium