J Mol Cell Cardiol 31, 377–386 (1999) Article No. jmcc.1998.0871, available online at http://www.idealibrary.com on Hypoxia-Reoxygenation and Polyunsaturated Fatty Acids Modulate Adrenergic Functions in Cultured Cardiomyocytes Philippe Delerive 1 , Fabien Oudot 2 , Blandine Ponsard 3 , Sylvie Talpin 1 , Jean Pierre Sergiel 1 , Catherine Cordelet 1 , Pierre Athias 3 and Alain Grynberg 2 1 Unite ´ de Nutrition Lipidique, INRA, 21034 Dijon, France; 2 INRA-UNHPI-UR914, Faculte ´ des Sciences Pharmacologiques et Biologiques, 75270 Paris, France and 3 LPPCE, Faculte ´ de me ´decine, 21034 Dijon, France (Received 27 April 1998, accepted in revised form 26 October 1998) P. D,F.O, B. P, S. T , J. P. S, C. C,P.A A. G. Hypoxia- Reoxygenation and Polyunsaturated Fatty Acids Modulate Adrenergic Functions in Cultured Cardiomyocytes. Journal of Molecular and Cellular Cardiology (1999) 31, 377–386. The polyunsaturated fatty acids (PUFAs) of the 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 - and - 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 -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 -adrenergic messenger production, and that the -system may balance the depression of the -system. The depression of the -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. 1999 Academic Press K W: Polyunsaturated fatty acids; Hypoxia; Cardiomyocyte; Adrenergic function; Membrane. disease prevention. This effect has been pro- Introduction gressively associated to a reduction of the incidence of atherosclerosis, based on several sites of inter- From the early epidemiological studies by Bang and Dyerberg (1972), dietary long-chain poly- vention of 3 PUFAs, including plasma cholesterol and triglycerides, regulation of the vascular tone, unsaturated fatty acids (PUFA) of the 3 series have been known for their contribution to cardiovascular blood pressure and platelet aggregation (Kinsella et Please address all correspondence to Alain Grynberg, INRA-UNHPI-UR914, Faculte ´ des Sciences Pharmacologiques et Biologiques, 4 Av de l’Observatoire, 75270 Paris, France. 0022–2828/99/020377+10 $30.00/0 1999 Academic Press