Loss of pacing-induced preconditioning in rat hearts: Role of nitric oxide and cholesterol-enriched diet

Péter Ferdinandy, Zoltán Szilvássy, László I. Horváth, Tamás Csont, Csaba Csonka, Erzsébet Nagy, Réka Szentgyörgyi, István Nagy, Matyas Koltai, László Dux

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Abstract

We examined whether the inhibition of nitric oxide (NO) synthesis by N(G)-nitro-L-arginine (LNNA) abolished pacing-induced preconditioning, and if prolonged exposure to cholesterol-enriched diet led to the loss of preconditioning due to decreased cardiac NO formation. Therefore, Wistar rats fed 2% cholesterol-enriched diet or standard diet for 24 weeks were treated with a single dose of 1 mg/kg LNNA or its solvent at the end of the week 24, respectively. Isolated hearts from all groups were subjected to either preconditioning induced by three consecutive periods of pacing at 600 beats/min for 5 min, with 5-min interpacing periods, or time-matched non-preconditioning perfusion, followed by a 10-min coronary occlusion, respectively. In the control group, coronary occlusion after a non-preconditioning protocol decreased aortic flow (AF) from 45.4 ± 2.4 to 15.6 ± 1.5 ml/min, and resulted in a lactate dehydrogenase (LDH) release of 219 ± 55 mU/min/g, however, preconditioning attenuated the consequences of coronary occlusion [AF: 27.3 ± 1.7 ml/min (P < 0.05); LDH: 44 ± 14 mU/min/g (P < 0.05)]. Preconditioning did not confer protection in the LNNA-treated (AF: 17.4 ± 1.5 ml/min; LDH: 151 ± 21 mU/min/g), and/or in the high-cholesterol-fed groups (AF: 15.7 ± 1.2 ml/min; LDH: 168 ± 22 mU/min/g). Preconditioning was preserved however, when hearts were treated with LNNA after the preconditioning protocol [AF: 29.6 ± 2.2 ml/min (P < 0.05); LDH: 48 ± 17 mU/min/g (P < 0.05)]. Both LNNA treatment and cholesterol-enriched diet markedly decreased cardiac NO content assayed by electron spin resonance spectroscopy. We conclude that NO may be involved in the triggering mechanism of pacing-induced preconditioning, the protective effect of which is blocked by sustained exposure to dietary cholesterol, possibly by influencing cardiac metabolism of NO.

Original languageEnglish
Pages (from-to)3321-3333
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 1997

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Keywords

  • Cardiac function
  • Cardioprotection
  • Coronary occlusion
  • Electron spin resonance
  • Hypercholesterolemia
  • N(G)-nitro-L-arginine
  • Nitric oxide
  • Rapid pacing

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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