title: Differential inhibition of renin mRNA expression by paricalcitol and calcitriol in C57/BL6 mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Integrative Pharmacology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6119, USA. ryan.fryer@abbott.com
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Fryer
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Rakestraw
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakane
authors.forename: Doug
authors.initials: D
authors.lastname: Dixon
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Banfor
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Koch
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Wu-Wong
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Reinhart
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004872:Ergocalciferols / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010281:Parathyroid Hormone / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004872:Ergocalciferols; D010281:Parathyroid Hormone; C084656:paricalcitol; D012083:Renin; D002117:Calcitriol; D002118:Calcium