Increased superoxide anion production is associated with early atherosclerosis and cardiovascular dysfunctions in a rabbit model.
OBJECTIVE
Hypercholesterolemia (HC) has been associated with impairment of vascular and myocardial functions. As HC could generate an alteration in the oxidative status, we studied the effects of a 1-month cholesterol diet on cardiovascular oxidative stress.


RESULTS
New Zealand rabbits received cholesterol (1%) or normal chow for 1 month. At 30 days, superoxide anion levels, assessed by ESR spectroscopy, NAD(P)H oxidase (NOX) activity, and dihydroethidium (DHE) staining of aortas were higher in the cholesterol-fed (CF) group compared with control (respectively, 4.0 +/- 0.6 Arbitrary Units/mg (AU/mg) vs. 2.6 +/- 0.3, p < 0.05; 4231 +/- 433 vs. 2931 +/- 373 AU/mg, p<0.05; 21.4 +/- 1.2 vs. 12.9 +/- 1.7% fluorescence/mm2, p < 0.001). NOX gp91 phox and p67 phox expression in the aortas were higher in the CF group vs. control (1.5 +/- 0.2 vs. 0.5 +/- 0.2, p < 0.001; 0.9 +/- 0.2 vs. 0.3 +/- 0.2, p<0.05). The endothelium-dependent relaxation evaluated on the iliac arteries was higher in control than in the CF group (64.8 +/- 10.1 vs. 13.1 +/- 3.70%, p<0.001). The cardiac diastolic pressure estimated on isolated hearts was higher in the CF group than in control (21.1 +/- 4.1 vs. 10.3 +/- 1.4 mmHg, p<0.05) after 60 min of ischemia.


CONCLUSIONS
Hypercholesterolemia induced increased levels of superoxide in the aortas and a higher expression of NOX subunits, associated with altered vasorelaxation. The increased diastolic pressure observed in hearts, consistent with a post-ischemic contractile dysfunction might be mediated by the production of superoxide.
Collin
Bertrand
B
Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology, Faculty of Medicine, University of Burgundy, 7, Boulevard Jeanne d'Arc, 21079, Dijon Cedex, BP 87900, France. bertrand.collin@voila.fr
Busseuil
David
D
Zeller
Marianne
M
Perrin
Caroline
C
Barthez
Olivier
O
Duvillard
Laurence
L
Vergely
Catherine
C
Bardou
Marc
M
Dumas
Monique
M
Cottin
Yves
Y
Rochette
Luc
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002319:Cardiovascular System / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D006651:Histocytochemistry; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology; D007083:Iliac Artery / Q000187:drug effects / Q000503:physiopathology; D049449:Luminescence; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000032:analysis; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D008076:Cholesterol, HDL; D014665:Vasodilator Agents; D013481:Superoxides; D002784:Cholesterol; D019255:NADPH Oxidases; D000109:Acetylcholine