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

Effects of paricalcitol and enalapril on atherosclerotic injury in mouse aortas.

Author information

1
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, P.R., USA. khusain@psm.edu

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.

PMID:
20720404
DOI:
10.1159/000319445
[Indexed for MEDLINE]

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