Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts

Annamária Ónody, C. Csonka, Z. Giricz, P. Ferdinándy

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119 Citations (Scopus)

Abstract

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 2×20 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.

Original languageEnglish
Pages (from-to)663-670
Number of pages8
JournalCardiovascular Research
Volume58
Issue number3
DOIs
Publication statusPublished - Jun 1 2003

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Peroxynitrous Acid
Hyperlipidemias
Cholesterol
Diet
Nitric Oxide Synthase
Superoxides
Blood Pressure
Xanthine Oxidase
Biological Availability
Superoxide Dismutase
Wistar Rats
Iron
Pathology
Proteins

Keywords

  • Cholesterol
  • Contractile function
  • Enzyme
  • Free radicals
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts. / Ónody, Annamária; Csonka, C.; Giricz, Z.; Ferdinándy, P.

In: Cardiovascular Research, Vol. 58, No. 3, 01.06.2003, p. 663-670.

Research output: Contribution to journalArticle

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