Myocardial production of prostaglandins: its role in atrial natriuretic peptide release

Azizi C, Barthélemy C, Masson F, Maistre G, Eurin J, Carayon A. Myocardial production of prostaglandins: its role in atrial natriuretic peptide release. Eur J Endocrinol 1995;133:255–9. ISSN 0804–4643 In recent years, considerable evidence has been accumulated on prostaglandins (PG) in modulating atrial natriuretic peptide (ANP) release. In the current study we investigated whether eicosanoids promote isoproterenol-induced ANP secretion from superfused rabbit sliced atria. Inclusion of the cyclooxygenase inhibitor indomethacin (10 μmol to the superfusing medium abolished isoproterenol-induced ANP release. Next, PGE2, but not PGF2α or PGI2 (10 μmol), increased ANP release. Furthermore, isoproterenol-induced PGE2 formation was fully attenuated by indomethacin. Dibutyl-cAMP (0.5 mmol) had no effect on PGE2 formation, and the protein kinase A (PKA) inhibitor H89 (20 μmol) did not alter isoproterenol-induced PGE2 formation. On the other hand, indomethacin led to a significant decrease in isoprotrenol-induced cAMP production. In addition, PGE2 enhanced basal cAMP concentration in superfusates. Superfusion of sliced atria by forskolin (10 μmol) or by dibutylcAMP (0.5 mmol) produced a significant rise in ANP release. Finally, H89 was ineffective on basal ANP release but abolished the increase of ANP release in response to isoproterenol or to PGE2. We conclude that: the effect of isoproterenol on ANP release is sensitive to indomethacin and H89; PGE2, but not PGF2α or PGI2, increases ANP release; isoproterenol promotes myocardial PGE2 formation independently of adenylate cyclase and PKA activation pathways; and PGE2-induced ANP release is mediated by cAMP production and subsequent PKA activation. These results suggest that isoproterenol-induced ANP release appears to be mediated at least partly by PGE2 with underlying cAMP formation and PKA activation. C Azizi, Service de Biochimie, CHU Pitié-Salpêtrère, 91 boulevard de l'hôpital, 75634 Paris Cedex 13, France