Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts.
OBJECTIVE
We investigated the influence of experimental hyperlipidemia on the formation of cardiac NO, superoxide, and peroxynitrite (ONOO(-)) in rat hearts.


METHODS
Wistar rats were fed 2% cholesterol-enriched diet or normal diet for 8 weeks. Separate groups of normal and hyperlipidemic rats were injected twice intraperitoneally with 2 x 20 micromol/kg FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), a ONOO(-) decomposition catalyst, 24 h and 1 h before isolation of the hearts.


RESULTS
A cholesterol diet significantly decreased myocardial NO content, however, myocardial Ca(2+)-dependent and Ca(2+)-independent NO synthase activity and NO synthase protein level did not change. Myocardial superoxide formation and xanthine oxidase activity were significantly increased; however, cardiac superoxide dismutase activity did not change in the cholesterol-fed group. Dityrosine in the perfusate, a marker of cardiac ONOO(-) formation, and plasma nitrotyrosine, a marker for systemic ONOO(-) formation, were both elevated in hyperlipidemic rats. In cholesterol-fed rats, left ventricular end-diastolic pressure (LVEDP) was significantly elevated as compared to controls. Administration of FeTPPS normalized LVEDP in the cholesterol-fed group.


CONCLUSIONS
We conclude that cholesterol-enriched diet-induced hyperlipidemia leads to an increase in cardiac ONOO(-) formation and a decrease in the bioavailability of NO which contributes to the deterioration of cardiac performance and may lead to further cardiac pathologies.
Onody
Annamária
A
Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary.
Csonka
Csaba
C
Giricz
Zoltán
Z
Ferdinandy
Péter
P
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006949:Hyperlipidemias / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood*; D014968:Xanthine Dehydrogenase / Q000032:analysis
D015415:Biomarkers; D002791:Cholesterol, Dietary; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C007543:dityrosine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase