Key result
Increasing n-3 PUFA in phospholipids reduced the increase in alpha- and beta-adrenergic functional responses observed after hypoxia-reoxygenation in rat cardiomyocytes.
Enrichment of cardiomyocyte membranes with n-3 PUFA attenuates the hyper-responsiveness to catecholamines following hypoxia-reoxygenation, suggesting a potential mechanism for their cardioprotective effects.
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n-3 PUFA enrichment blunts post-reoxygenation adrenergic hyperresponsiveness in rat cardiomyocytes; hypothesis-generating, requires human validation before clinical consideration.
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 alpha- and beta-adrenoceptor (alpha-AR, beta-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 beta-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 alpha- and beta-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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Ponsard et al. (1999) studied Ischemia-reperfusion (hypoxia-reoxygenation model). n-3 PUFA (EPA and DHA) enriched media vs. n-6 PUFA (AA) enriched media was evaluated on Chronotropic response to alpha- and beta-adrenoceptor activation after hypoxia-reoxygenation. Increasing n-3 PUFA in phospholipids reduced the increase in alpha- and beta-adrenergic functional responses observed after hypoxia-reoxygenation in rat cardiomyocytes.
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