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Cross-influence of membrane polyunsaturated fatty acids and hypoxia-reoxygenation on α- and β-adrenergic function of rat cardiomyocytes

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Lipids

Abstract

The purpose of the present investigation was to determine whether the beneficial effects of polyunsaturated fatty acids (PUFA) may influence ischemia-reperfusion-induced alterations of myocardial α- and β-adrenoceptor (α-AR, β-AR) responsiveness. This study was carried out using monolayer cultures of neonatal rat ventricular myocytes in a substrate-free, hypoxia-reoxygenation model of ischemia. The cardiomyocytes (CM) were incubated during 4 days in media enriched either with n−6 PUFA (arachidonic acid, AA) or with n−3 PUFA (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA). The n−6/n−3 ratio in n−3 CM was close to 1.2, compared to 20.1 in n−6 CM. The contractile parameters of n−6 CM and n−3 CM were similar in basal conditions as well as during hypoxia and reoxygenation. In basal conditions, the phospholipid (PL) enrichment with long chain n−3 PUFA resulted in an increased chronotropic response to isoproterenol (ISO) and to phenylephrine (PHE). After posthypoxic reoxygenation, the chronotropic response to β-AR activation in n−6 CM was significantly enhanced as compared with the control response in normoxia. In opposition, the ISO-induced rise in frequency in n−3 CM in control normoxia and after reoxygenation was similar. In these n−3 CM, the changes in contractile parameters, which accompanied the chronotropic response, were also similar in reoxygenation and in normoxic periods, although the rise in shortening velocity was slightly increased after reoxygenation. In response to PHE addition, only the chronotropic effect of n−6 CM appeared significantly enhanced after hypoxic treatment. These results suggested that increasing n−3 PUFA in PL reduced the increase in α- and β-AR functional responses observed after hypoxia-reoxygenation. This effect may partly account for the assumed cardiac protective effect of n−3 PUFA, through the attenuation of the functional response to catecholamines in the ischemic myocardium.

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Abbreviations

AA:

arachidonic acid

ANOVA:

analysis of variance

AR:

adrenoceptor

CD20:

duration at 20% contraction amplitude from peak contraction

CD80:

the duration at 80% contraction amplitude from peak contraction

CM:

cardiomyocytes

+Cmax:

time for 20–80% shortening

−Cmax:

time for 20–80% relaxation

CR:

contraction rate

DHA:

docosahexaenoic acid

EPA:

eicosanentaenoic acid

ISO:

isoproterenol

PHE:

phenylephrine

PL:

phospholipids

PUFA:

polyunsaturated fatty acids

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Authors and Affiliations

  1. Institut de Recherche Cardio-Vasculaire, Centre Hospitalier Universitaire, 21034, Dijon, France

    Blandine Ponsard, Isabelle Durot & Pierre Athias

  2. Unité de Nutrition Lipidique, INRA, Dijon, France

    Philippe Delerive & Catherine Cordelet

  3. Lipides Membranaires et Fonctions Cardiovasculaires, Faculté des Sciences Pharmaceutiques et Biologiques, INRA-UNHPI-UR 914, 75270, Paris Cedex 06, France

    Fabien Oudot & Alain Grynberg

Authors
  1. Blandine Ponsard
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  2. Isabelle Durot
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  3. Philippe Delerive
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  4. Fabien Oudot
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  5. Catherine Cordelet
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  6. Alain Grynberg
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  7. Pierre Athias
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Correspondence to Pierre Athias.

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Ponsard, B., Durot, I., Delerive, P. et al. Cross-influence of membrane polyunsaturated fatty acids and hypoxia-reoxygenation on α- and β-adrenergic function of rat cardiomyocytes. Lipids 34, 457–466 (1999). https://doi.org/10.1007/s11745-999-0385-5

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  • DOI: https://doi.org/10.1007/s11745-999-0385-5

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