Classic preconditioning decreases the harmful accumulation of nitric oxide during ischemia and reperfusion in rat hearts

C. Csonka, Z. Szilvássy, F. Fülöp, T. Páli, Ingolf E. Blasig, A. Tósaki, Richard Schulz, P. Ferdinándy

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Abstract

Background - The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results - Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes' duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 μmol/L N(G)-nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/repel fusion-induced functional depression and NO accumulation were abolished. When 4.6 μmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 μmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions - Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.

Original languageEnglish
Pages (from-to)2260-2266
Number of pages7
JournalCirculation
Volume100
Issue number22
Publication statusPublished - Nov 30 1999

Fingerprint

Reperfusion
Nitric Oxide
Ischemia
Nitric Oxide Synthase
Myocardial Reperfusion
Electron Spin Resonance Spectroscopy
Reperfusion Injury
Arginine

Keywords

  • Electron spin resonance
  • Ischemia
  • Nitric oxide
  • Preconditioning
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Classic preconditioning decreases the harmful accumulation of nitric oxide during ischemia and reperfusion in rat hearts",
abstract = "Background - The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results - Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes' duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 μmol/L N(G)-nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/repel fusion-induced functional depression and NO accumulation were abolished. When 4.6 μmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 μmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions - Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.",
keywords = "Electron spin resonance, Ischemia, Nitric oxide, Preconditioning, Reperfusion",
author = "C. Csonka and Z. Szilv{\'a}ssy and F. F{\"u}l{\"o}p and T. P{\'a}li and Blasig, {Ingolf E.} and A. T{\'o}saki and Richard Schulz and P. Ferdin{\'a}ndy",
year = "1999",
month = "11",
day = "30",
language = "English",
volume = "100",
pages = "2260--2266",
journal = "Circulation",
issn = "0009-7322",
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TY - JOUR

T1 - Classic preconditioning decreases the harmful accumulation of nitric oxide during ischemia and reperfusion in rat hearts

AU - Csonka, C.

AU - Szilvássy, Z.

AU - Fülöp, F.

AU - Páli, T.

AU - Blasig, Ingolf E.

AU - Tósaki, A.

AU - Schulz, Richard

AU - Ferdinándy, P.

PY - 1999/11/30

Y1 - 1999/11/30

N2 - Background - The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results - Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes' duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 μmol/L N(G)-nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/repel fusion-induced functional depression and NO accumulation were abolished. When 4.6 μmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 μmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions - Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.

AB - Background - The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results - Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes' duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 μmol/L N(G)-nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/repel fusion-induced functional depression and NO accumulation were abolished. When 4.6 μmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 μmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions - Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.

KW - Electron spin resonance

KW - Ischemia

KW - Nitric oxide

KW - Preconditioning

KW - Reperfusion

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C2 - 10578001

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