PROSTAGLANDIN-F2-ALPHA MEDIATES PLATELET-ACTIVATING FACTOR-STIMULATEDATRIAL-NATRIURETIC-FACTOR RELEASE FROM THE ISOLATED RAT-HEART

Platelet-activating factor (PAF) and the prostaglandins have recently been shown to stimulate atrial natriuretic factor (ANF) secretion from the heart. As PAF also potentiates the release of cyclooxygenase prod ucts from isolated hearts, the role of these substances in PAF-induced ANF secretion was investigated. Using an isolated perfused rat heart preparation, cyclooxygenase inhibition by indomethacin or meclofenamic acid (10 muM for each) significantly attenuated the rise in ANF assoc iated with PAF administration (2.5 nmol). Prostaglandin F2alpha (PGF) produced an immediate and dose-dependent increase in ANF secretion, wh ich was significant at 0.01 mumol and reached 348 +/- 66% over baselin e values after a 1-mumol injection. Prostaglandin E2 (PGE) generated a much smaller 98 +/- 25% increase after a 1-mumol administration. Furt hermore, PGF but not PGE was released from isolated hearts immediately after PAF administration. PGF release reached a maximum of 0.06 nmol/ min g Heart-11 min after PAF stimulation and had returned to undetecta ble baseline values by 6 min. Cyclooxygenase inhibition abolished the release of PGF after PAF, in addition to attenuating (by 60-70%) the i ncreased secretion of ANF after PAF injection. These results demonstra te very clearly that PGF is the major mediator for PAF-stimulated ANF secretion. Such an interaction may provide an alternative mechanism to atrial distension for the secretion of ANF in pathologies such as myo cardial infarction, where autacoids such as PAF and the PGs are releas ed from damaged cardiac muscle and elevated plasma levels of ANF are o bserved.