© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts
Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary
* Corresponding author. Tel.: +36-62-545-755; fax: +36-62-545-097. peter{at}bioch.szote.u-szeged.huhttp://www.cardiovasc.com
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 2x20 µmol/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 Ca2+-dependent and Ca2+-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. Conclusion: 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.
KEYWORDS Cholesterol; Contractile function; Enzyme; Free radicals; Nitric oxide
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