Arterial Calcifications in Uraemic Rats Treated with 1-α-Hydroxycholecalciferol and Parathyroidectomy

Abstract

The effect of 1-α-hydroxycholecalciferol (1-α-OH-D₃) on the incidence of arterial calcifications, and the influence of parathyroidectomy on the effect of this vitamin D treatment, were studied in uraemic rats. Uraemia was induced by ¾ kidney resection, and parathyroidectomy was achieved by electrocoagulation. 1-α-OH-D₃ in a dose of 3, 10 or 125 ng/100 g body weight (b.w.) was given in the drinking water. The animals were killed after 12 or 16 weeks. Aorta and small arteries in the heart and in anterior tibial muscle were studied by light microscopy. Arterial lesions were frequently found in uraemic rats and were characterized by medial necrosis and calcifications. Following a 1-α-OH-D₃ dose of 125 ng/100 g b.w. in uraemic rats both serum calcium and serum phosphate were increased and there was a high incidence of arterial calcifications both in the aorta and the small arteries. In uraemic rats receiving 10 ng/100 g b.w. of 1-α-OH-D₃ serum calcium was only slightly elevated although the incidence of arterial calcifications (mainly in the aorta) was much higher than in uraemic rats without vitamin-D treatment. A dose of 3 ng/100 g b.w. of 1-α-OH-D₃ given to uraemic rats did not result in any serum calcium increase, nor did it alter the incidence of arterial calcifications. Parathyroidectomy prevented arterial calcification in uraemic rats, but this effect was abolished by 1-α-OH-D₃ in a dose of 10 ng/100 g b.w. which only raised the serum calcium to a subnormal value. In uraemia, treatment with 1-α-OH-D₃ may increase the serum calcium × phosphate product, but this cannot fully explain the increased incidence of arterial calcifications. It is therefore suggested that vitamin D causes changes in the arterial wall which increase its susceptibility to the development of calcifications.