Hypoxia-reoxygenation and polyunsaturated fatty acids modulate adrenergic functions in cultured cardiomyocytes

The polyunsaturated fatty acids (PUFAs) of the omega 3 series are known to modulate adrenergic functions in ventricular myocytes. This study evaluated the influence of hypoxia duration and PUFA composition on the ability of c ultured rat cardiomyocytes in producing alpha- and beta-adrenergic messenge rs (IPs and cAMP). After hypoxia (1.5, 2.5 or 3.5 h) followed by reoxygenat ion (1h), IT and cAMP production was induced by phenylephrine or isoprotere nol stimulation, respectively. Hypoxia did not affect the basal level of me ssenger production in unstimulated cells, but decreased the cAMP production elicited by isoproterenol stimulation (up to 50%). The decrease in IP prod uction after phenylephrine stimulation was observed only after long-term hy poxia duration close to irreversible cellular damages. The use of modified culture media supplemented with either arachidonic acid (AA) or docosahexae noic acid (DHA) induced cardiomyocytes displaying either an arachidonic aci d membrane profile (35% AA and 2% DHA in the phospholipids) or a docosahexa enoic acid membrane profile (15% AA and 20% DHA). These modifications did n ot alter the basal level of either messenger production in unstimulated cel ls nor the IP released after alpha-adrcnergic stimulation, Conversely the d ecrease in cAMP production was significantly more pronounced in docosahexae noic acid-enriched cells than in arachidonic acid-enriched cells. This stud y suggests that hypoxia alters the beta-adrenergic messenger production, an d that the alpha-system may balance the depression of the beta-system. The depression of the beta-adrenergic function induced by the incorporation of docosahexaenoic acid in membrane phospholipids may contribute to the benefi cial effect of this fatty acid in the reperfused heart. (C) 1999 Academic P ress.