Modulation by prostaglandins of the release of [3H]noradrenaline evoked by potassium and nerve stimulation in the isolated rat heart

In the isolated rat heart perfused with Krebs solution and prelabeled with [³H]noradrenaline, we examined the effect of prostaglandins (PG) I₂, E₂, 6-keto-PGF_1α and their precursor, arachidonic acid, on the overflow of tritium elicited by potassium (K⁺) and by stimulation of cardiac sympathetic nerve plexus. Prostaglandins E₂, I₂ and arachidonic acid but not 6-keto-PGF_1α reduced K⁺ and nerve stimulation-induced overflow of tritium. Administration of indomethacin, an inhibitor of cyclooxygenase, increased tritium overflow elicited by either K⁺ or by nerve stimulation. During infusion of indomethacin, the inhibitory effect of both PGE₂ and PGI₂ on the K⁺ or nerve stimulation-induced overflow of tritium remained unaltered. In contrast, the effect of arachidonic acid to reduce K⁺ or nerve stimulation-induced overflow of tritium was abolished by indomethacin, indicating that the fatty acid inhibits release of tritium by its conversion to a product(s) of cyclooxygenase, presumably PGI₂ and PGE₂. These data suggest that prostaglandins, particularly PGI₂ and PGE₂ sythesized in the isolated rat heart act on prejunctional sites to modulate release of the adrenergic transmitter.