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 cultured rat cardiomyocytes in producing alpha- and beta-
adrenergic messengers (IPs and cAMP). After
hypoxia (1.5, 2.5 or 3.5 h) followed by reoxygenation (1h). IP and cAMP production was induced by
phenylephrine or
isoproterenol stimulation, respectively.
Hypoxia did not affect the basal level of messenger production in unstimulated cells, but decreased the cAMP production elicited by
isoproterenol stimulation (up to 50%). The decrease in IP production after
phenylephrine stimulation was observed only after long-term
hypoxia duration close to irreversible cellular damages. The use of modified
culture media supplemented with either
arachidonic acid (AA) or
docosahexaenoic acid (DHA) induced cardiomyocytes displaying either an
arachidonic acid membrane profile (35% AA and 2% DHA in the
phospholipids) or a
docosahexaenoic acid membrane profile (15% AA and 20% DHA). These modifications did not alter the basal level of either messenger production in unstimulated cells nor the IP released after alpha-
adrenergic stimulation. Conversely, the decrease in cAMP production was significantly more pronounced in
docosahexaenoic acid-enriched cells than in
arachidonic acid-enriched cells. This study suggests that
hypoxia alters the beta-
adrenergic messenger production, and 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 beneficial effect of this
fatty acid in the reperfused heart.