Effects of paricalcitol and enalapril on atherosclerotic injury in mouse aortas

Am J Nephrol. 2010;32(4):296-304. doi: 10.1159/000319445. Epub 2010 Aug 17.

Abstract

Aims: This study investigated the protective effect of vitamin D analog paricalcitol combined with angiotensin-converting enzyme inhibitor (enalapril) on aortic oxidative injury in atherosclerotic mice.

Methods: Female mice were treated for 16 weeks as follows: (1) ApoE deficient + vehicle, (2) ApoE deficient + paricalcitol (200 ng 3 times a week), (3) ApoE deficient + enalapril (30 mg/l in drinking water), (4) ApoE deficient + paricalcitol + enalapril, and (5) wild-type controls.

Results: ApoE-deficient mice developed hypertension which was prevented by enalapril or enalapril + paricalcitol treatment but not by paricalcitol treatment. Histology showed atherosclerotic plaque in the aorta of ApoE-deficient mice which was prevented by paricalcitol, enalapril, and paricalcitol + enalapril treatments. Aortic malondialdehyde levels, NADPH oxidase subunit p22(phox), manganese-superoxide dismutase (Mn-SOD), inducible nitric oxide synthase, monocyte chemoattaractant protein-1, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 protein expressions increased, whereas glutathione levels, CuZn-SOD, and endothelial protein expressions decreased in ApoE-deficient mice compared to controls. Treatment with paricalcitol and enalapril alone or in combination protected the inflammatory and oxidative endothelial injury of the aorta in atherosclerotic mice.

Conclusion: Combination therapy affords greater protection against aortic inflammatory and oxidative injury in atherosclerosis than monotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Aorta / physiopathology*
  • Apolipoproteins E / deficiency
  • Atherosclerosis / prevention & control*
  • Blood Pressure / drug effects
  • Chemokine CCL2 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Enalapril / pharmacology
  • Enalapril / therapeutic use*
  • Endothelium / metabolism
  • Ergocalciferols / pharmacology
  • Ergocalciferols / therapeutic use*
  • Female
  • Glutathione / metabolism
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Knockout
  • NADPH Oxidases / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / drug effects
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamins / pharmacology
  • Vitamins / therapeutic use*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Apolipoproteins E
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Ergocalciferols
  • Tumor Necrosis Factor-alpha
  • Vitamins
  • Malondialdehyde
  • paricalcitol
  • Enalapril
  • Nitric Oxide Synthase
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • NADPH Oxidases
  • Glutathione