REQUIREMENT FOR PROSTAGLANDIN SYNTHESIS IN SECRETION OF ATRIAL-NATRIURETIC-FACTOR FROM ISOLATED RAT-HEART

Release of atrial natriuretic factor (ANF) from the heart is primarily affected by myocyte stretch. In addition, ANF release can be modulate d by a variety of hormones and neurotransmitters, but the mechanisms i nvolved in such modulation are not completely understood. In the prese nt study, we investigated the effect of inhibition of cyclooxygenase a ctivity on release of ANF from the isolated, spontaneously beating rat heart: (1) during basal conditions; and (2) in response to arginine v asopressin (AVP), acetylcholine (ACh) and angiotensin II (ANG II), in order to determine if cardiac prostaglandin synthesis is involved in m odulation of basal and hormone-mediated ANF secretion. Basal secretion in the time controls remained stable for the duration of the experime nt. AVP, ACh and ANG II reduced basal secretion significantly by 58 +/ - 4%, 51 +/- 6% and 26 +/- 8%, respectively, independently of concomit ant changes in coronary flow and heart rate. Inhibition of cyclooxygen ase with indomethacin (1 . 10(-5) M) decreased basal ANF release by 38 +/- 6%, indicating that basal secretion requires prostaglandin produc tion. The effects of AVP, ACh and ANG II were maintained during perfus ion with indomethacin, suggesting a common mechanism of action which o perates via inhibition of cyclooxygenase. Based on our previous findin gs that the effects of indomethacin, AVP and ACh are overcome by inhib ition of NO/EDRF synthesis, we suggest a common mechanism of action by means of which NO/EDRF mediates the effects of these agents by inhibi ting cyclooxygenase activity.