Effect of 22-oxa-calcitriol on calcium metabolism in rats with severe secondary hyperparathyroidism

Abstract

The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 μg i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 μg i.p./rat) or calcitriol (0.05 μg i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 ± 0.04 and 1.10 ± 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 ± 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 ± 0.4 to 7.0 ± 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 ± 75 pg/ml (calcitriol) versus 632 ± 46 pg/ml (OCT) compared with 897 ± 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 μg i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 μg i.p./rat) in reducing circulating iPTH: 110 ± 26 (calcitriol) and 281 ± 64 (OCT) versus 624 ± 135 pg/ml (control), P < 0.01. The same tendency was observed for both compounds regarding the increase in blood Ca2+: 1.36 ± 0.04 (calcitriol) and 1.26 ± 0.04 (OCT) versus 1.05 ± 0.06 mM (control), P < 0.01. S/M was significantly increased by calcitriol but not by OCT: 4.0 ± 0.3 (calcitriol) versus 3.0 ± 0.09 (OCT) versus 2.6 ± 0.3 (control), P < 0.05. In conclusion, in this model of secondary hyperparathyroidism, OCT as well as calcitriol treatment increased blood Ca2+ and decreased circulating iPTH levels. However, the effects of OCT on both parameters were less marked than those of calcitriol. Both vitamin D derivatives were equivalent in increasing duodenal calbindin-D9K mRNA and protein synthesis, but only calcitriol stimulated intestinal calcium transport.