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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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Dietary polyunsaturated fatty acids (PUFA) have been reported to lower the incidence of cardiovascular diseases, but neither the mechanisms that determine these protective effects nor the specific influence of n-3 vs. n-6 PUFA series has been well established. The purpose of this work was to demonstrate the influence of the membrane long-chain fatty acid composition on the spontaneous contractile activity and the adrenergic function of rat cardiomyocytes in culture. Cells were grown for 24 h in a standard culture medium and then for 4 d in media that contained either n-3 (eicosapentaenoic acid and docosahexaenoic acid) or n-6 (arachidonic acid) PUFA. The n-6/n-3 ratio was 1.2 in n-3 cells compared with 20.1 in n-6 cells. The basal contractile properties of these cardiomyocytes were not affected by the PUFA phospholipid composition. However, these modifications influenced the adrenoceptor function because the β-adrenergic stimulation by isoproterenol (10 −7 M) induced a positive chronotropic response that was significantly greater in n-3 cells. Moreover, the chronotropic response to α-adrenoceptor stimulation by phenylephrine (10 −6 M) appeared significantly more pronounced in the n-3 cells than in the n-6 cells. However, the parameters related to the inotropic response induced by these agonists did not differ significantly between the two groups of cells. These results suggested that the membrane long-chain PUFA composition does not influence the basal cardiac contractility and automaticity but is able to modulate the chronotropic function of both α-and β-adrenoceptors. JAOCS 75, 247-254 (1998).