PROGRESSION AND REGRESSION BY VERAPAMIL OF VITAMIN-D-3-INDUCED CALCIFIC MEDIAL DEGENERATION IN CORONARY-ARTERIES OF RATS

Vitamin D-3-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 dege neration in coronary arteries of rats after one intoxication with vita min D-3 was examined, as well as possible regression of preestablished mural Ca overload with the Ca antagonist verapamil, Sprague-Dawley ra ts were treated with one intramuscular (i.m.) overdose of vitamin D-3 [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 D-3 int oxication, Arteriosclerotic alterations were verified by microchemical analyses of tissue Ca and of cholesterol contents with atomic absorpt ion spectroscopy (special graphite tube technique) and gas chromatogra phy, respectively, and by standard histological techniques. Serum lipi ds were determined by sequential ultracentrifugation. Between week 3 a nd week 26 after the vitamin D-3 injection, a progressive Ca incorpora tion from 448.8 +/- 110 to 1,310 +/- 166.3% of control values (i.e., c oronary Ca content in 32-week-old untreated control rats = 100%) was o bserved, associated with calcific morphological lesions, and reactive intimal plaque formation. Verapamil prevented this progression and ind uced 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 ca lcific lesion of coronary arteries may serve as crystallization nucleu s for advancing Ca overload and morphological alterations. Damping of transmembrane Ca influx into vascular smooth muscle cells by verapamil , possibly in concert with a direct interaction of verapamil with extr acellular Ca binding sites, halts progression and obviously favors hea ling processes responsible for the regression of preestablished lesion s.