Differential Inhibition of Renin MRNA Expression by Paricalcitol and Calcitriol in C57/BL6 Mice

Background/aims: Vitamin D receptor activators (VDRAs) may suppress renin expression and VDR-mediated renin inhibitors may offer a novel mechanism to control the RAS.

Methods: We delineated the effects of paricalcitol and calcitriol on PTH, renin, and iCa(2+) in C57/BL6 mice administered vehicle, paricalcitol, or calcitriol (0.01, 0.03, 0.10, 0.33, 1.0 microg/kg s.c.) 3 days/week for 9 days.

Results: Paricalcitol produced PTH suppression from 0.03 to 1.0 microg/kg (values between 9.7 +/- 3.3 and 20.7 +/- 4.7 pg/ml; vehicle = 88.0 +/- 16.9) and elicited dose-dependent reductions in renin/GAPDH expression at 0.33 and 1.0 microg/kg (0.037 +/- 0.002, 0.027 +/- 0.003; vehicle = 0.054 +/- 0.003) but produced no increases iCa(2+) at any dose tested. Calcitrol produced PTH suppression at all doses tested (between 6.4 +/- 1.2 and 29.5 +/- 17.2 pg/ml) and renin suppression at 0.10, 0.33, and 1.0 microg/kg (0.029 +/- 0.002, 0.031 +/- 0.003, and 0.038 +/- 0.02). However, at 0.33 and 1.0 mg/kg, calcitriol produced increases iCa(2+) (1.31 +/- 0.03 and 1.48 +/- 0.02 mmol/l; vehicle = 1.23 +/- 0.02 mmol/l).

Conclusions: Paricalcitol produces significant, dose-dependent suppression of renin expression in the absence of hypercalcemia at doses 10-fold above those necessary for PTH suppression. Calcitriol also produced suppression of renin at doses at least 10-fold above those required for PTH suppression, but increases in iCa(2+) were observed at doses only 3-fold above those necessary to elicit renin suppression.