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 modulated by a variety of hormones and neurotransmitters, but the mechanisms involved in such modulation are not completely understood. In the present study, we investigated the effect of inhibition of cyclooxygenase activity on release of ANF from the isolated, spontaneously beating rat heart: (1) during basal conditions; and (2) in response to arginine vasopressin (AVP), acetylcholine (ACh) and angiotensin II (ANG II), in order to determine if cardiac prostaglandin synthesis is involved in modulation of basal and hormone-mediated ANF secretion. Basal secretion in the time controls remained stable for the duration of the experiment. AVP, ACh and ANG II reduced basal secretion significantly by 58 +/- 4%, 51 +/- 6% and 26 +/- 8%, respectively, independently of concomitant changes in coronary flow and heart rate. Inhibition of cyclooxygenase with indomethacin (1 x 10(-5) M) decreased basal ANF release by 38 +/- 6%, indicating that basal secretion requires prostaglandin production. The effects of AVP, ACh and ANG II were maintained during perfusion with indomethacin, suggesting a common mechanism of action which operates via inhibition of cyclooxygenase. Based on our previous findings that the effects of indomethacin, AVP and ACh are overcome by inhibition of NO/EDRF synthesis, we suggest a common mechanism of action by means of which NO/EDRF mediates the effects of these agents by inhibiting cyclooxygenase activity.