Hypoxia-Reoxygenation and Polyunsaturated Fatty Acids Modulate Adrenergic Functions in Cultured Cardiomyocytes

• Published in: Journal of molecular and cellular cardiology 1999-02, Vol.31 (2), p.377-386
• Main Authors: Delerive, Philippe, Oudot, Fabien, Ponsard, Blandine, Talpin, Sylvie, Sergiel, Jean Pierre, Cordelet, Catherine, Athias, Pierre, Grynberg, Alain
• Format: Article
• Language: English
• Subjects: Adrenergic function; Animals; Cardiomyocyte; Cell Hypoxia; Cells, Cultured; Fatty Acids, Unsaturated - metabolism; Hypoxia; Intracellular Fluid - metabolism; Membrane; Myocardium - cytology; Oxygen; Phospholipids - metabolism; Polyunsaturated fatty acids; Rats; Rats, Wistar; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, beta - metabolism
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1998.0871

The polyunsaturated fatty acids (PUFAs) of theω3 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 producingα- andβ-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 afterα-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 theβ-adrenergic messenger production, and that theα-system may balance the depression of theβ-system. The depression of theβ-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.