Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats.
Vitamin D3-induced mural calcification represents an animal model for investigating experimental calcium (Ca) overload and calcification of arterial walls. In this study, long-term progression of calcific degeneration in coronary arteries of rats after one intoxication with vitamin D3 was examined, as well as possible regression of preestablished mural Ca overload with the Ca antagonist verapamil. Sprague-Dawley rats were treated with one intramuscular (i.m.) overdose of vitamin D3 [300,000 IU/kg body weight (b.w.)]. Oral verapamil therapy (100 mg/kg/day b.w. for 24 weeks) was initiated 14 days after the vitamin D3 intoxication. Arteriosclerotic alterations were verified by microchemical analyses of tissue Ca and of cholesterol contents with atomic absorption spectroscopy (special graphite tube technique) and gas chromatography, respectively, and by standard histological techniques. Serum lipids were determined by sequential ultracentrifugation. Between week 3 and week 26 after the vitamin D3 injection, a progressive Ca incorporation from 448.8 +/- 110 to 1,310 +/- 166.3% of control values (i.e., coronary Ca content in 32-week-old untreated control rats = 100%) was observed, associated with calcific morphological lesions, and reactive intimal plaque formation. Verapamil prevented this progression and induced a regression of preestablished mural Ca overload. Therefore, the coronary Ca content after 24 weeks of verapamil treatment amounted to only 146.3 +/- 53.8% of controls. The data indicate that an initial calcific lesion of coronary arteries may serve as crystallization nucleus for advancing Ca overload and morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy; D002114:Calcinosis / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002762:Cholecalciferol / Q000633:toxicity*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D008055:Lipids; D002762:Cholecalciferol; D014700:Verapamil; D002118:Calcium