Aortic Calcification Produced by Vitamin D ₃ plus Nicotine

Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 +/- 87, n = 12 in VDN vs. 24 +/- 2 micromol g(-1) aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 +/- 17 and 254 +/- 15 in VDN vs. 655 +/- 56 and 588 +/- 30 microg g(-1) aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 +/- 1.8 in VDN vs. 6.7 +/- 0.5 10(6) dyn cm(-2) in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 +/- 6 in VDN vs. 136 +/- 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 +/- 0.10 in VDN vs. 2.24 +/- 0.07 g kg(-1) in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero- and arteriosclerosis.