Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite.

Full Abstract

The aim of the present study was to investigate if hyperlipidemia interferes with the infarct size-limiting effect of postconditioning and to study the involvement of peroxynitrite in this phenomenon. Rats were fed a 2% cholesterol-enriched or normal diet for 12 wk. Infarct size by triphenyltetrazolium chloride staining was measured in hearts isolated from both groups and subjected to 30 min coronary occlusion followed by 120 min reperfusion with or without the postconditioning protocol induced by six cycles of 10 s coronary occlusion and 10 s reperfusion at the onset of the reperfusion. Postconditioning significantly decreased infarct size in the normolipidemic but not in the hyperlipidemic group. Postconditioning increased cardiac 3-nitrotyrosine concentration (a marker for peroxynitrite formation) in the normal but not in the cholesterol-fed group when measured at the 5th min of reperfusion. Next, we tested if the postconditioning-induced acute increase in peroxynitrite is involved in the cardioprotection in normolipidemic animals in separate experiments. Postconditioning failed to decrease infarct size in the presence of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron [III] (20 mg/l) in normolipidemic animals. We conclude that an early increase in peroxynitrite after postconditioning plays a role in cardioprotection. Furthermore, hyperlipidemia blocks the cardioprotective effect of postconditioning at least in part via deterioration of the postconditioning-induced early increase in peroxynitrite formation.

Author information

Author/s: Kupai, Krisztina (K); Csonka, Csaba (C); Fekete, Veronika (V); Odendaal, Louise (L); van Rooyen, Jacques (J); Marais, De Wet (de W); Csont, Tamás (T); Ferdinandy, Péter (P);

Affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol), published in United States. (Language: eng)

Reference: 2009-Nov; vol 297 (issue 5) : pp H1729-35

Dates: Created 2009/10/27; Completed 2009/11/12;

PMID: 19734363, status: MEDLINE (last retrieved date: 11/12/2009)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Biological Markers - metabolism
Cholesterol, Dietary - adverse effects
Disease Models, Animal
Hyperlipidemias - complications; etiology; metabolism; pathology
Male
Metalloporphyrins - pharmacology
Myocardial Infarction - etiology; metabolism; pathology; prevention & control

Myocardial Infarction - etiology; metabolism; pathology; prevention & control
Myocardial Reperfusion Injury - etiology; metabolism; pathology; prevention & control
Myocardium - metabolism; pathology
Peroxynitrous Acid - metabolism
Rats
Signal Transduction
Stress, Physiological - drug effects
Tyrosine - analogs & derivatives; metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride (0) ; Biological Markers (0) ; Cholesterol, Dietary (0) ; Metalloporphyrins (0) ; Peroxynitrous Acid (14691-52-2) ; 3-nitrotyrosine (3604-79-3) ; Tyrosine (55520-40-6)

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