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


CONCLUSIONS
Combination therapy affords greater protection against aortic inflammatory and oxidative injury in atherosclerosis than monotherapy.
Husain
Kazim
K
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, P.R., USA. khusain@psm.edu
Suarez
Edu
E
Isidro
Angel
A
Ferder
Leon
L
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D004727:Endothelium / Q000378:metabolism; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004872:Ergocalciferols; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D008315:Malondialdehyde; C084656:paricalcitol; D004656:Enalapril; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005978:Glutathione