Prostaglandin actions and interactions on isolated perfused rat hearts

Abstract

The actions of prostaglandins (PGs) D2, E1, E2, F2α, and I2 and interactions between these agents were examined using the isolated Langendorff-perfused rat heart. In concentrations between 2.8 × 10−11 and 2.8 × 10−7 M, PGE2, PGD2, and PGF2α produced an increase in coronary perfusion pressure while PGE1 addition resulted in a decrease. The PGI2 constricted the coronary vessels at 2.8 × 10−10 M although higher concentrations resulted in dilatation. The PGF2α produced significant increases in the contractile force but negative inotropic effects were seen with PGE1. The PGI2 actions on myocardial contractility were biphasic. Variable changes were seen with regard to resting tension after PG administration. Complex interactions were noted when PGs were examined in the presence of other PGs or arachidonic acid. Prior addition of either PGE2 (2.8 × 10−10 M) or arachidonic acid (2.8 × 10−7 M) inhibited or reversed various actions of PGD2 on the heart. The coronary and myocardial effects of PGE1 were usually influenced by the presence of most other PGs as well as arachidonic acid. Arachidonic acid, PGF2α, and PGE1 attenuated the coronary constricting and positive inotropic actions of PGE2. The PCL1 reversed the positive inotropic effects of PGF2α. When added alone, PGI2 had slight coronary-constricting actions but in the presence of other agents a biphasic effect was seen. The PGI2 increased the myocardial contractile force significantly only in the presence of PGF2α. These results suggest diverse actions of PGs within a wide concentration range and suggest that PG actions may be influenced by the presence of other PG substances.