Effects of Paricalcitol and Enalapril on Atherosclerotic Injury in Mouse Aortas

• Published in: American journal of nephrology Vol. 32; no. 4; pp. 296 - 304
• Main Authors: Husain, Kazim, Suarez, Edu, Isidro, Angel, Ferder, Leon
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2010
• Subjects: 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; Original Report: Laboratory Investigation; Oxidative Stress - drug effects; Superoxide Dismutase - metabolism; Tumor Necrosis Factor-alpha - metabolism; Vitamins - pharmacology; Vitamins - therapeutic use; Renin-angiotensin system; Monocyte chemoattractant protein-1; Glutathione
• ISSN: 0250-8095; 1421-9670
• DOI: 10.1159/000319445

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.