Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ - K+ stimulated ATPase activity.

The actions of thromboxane B2 on various parameters of cardiac performance were studied using the isolated perfused rat heart model. In concentrations from 100 pg/ml to 1 microgram/ml TXB2 significantly reduced the total generated myocardial contractile force. These changes were usually associated with an increase in the coronary perfusion pressure indicating an elevated coronary vascular resitance. Significant coronary pressure alterations were seen with TXB2 concentrations between 1 ng/ml and 1 microgram/ml. No significant changes were seen in either the resting tension or heart rate after TXB2 administration. However TXB2 (10 pg/ml to 10 ng/ml,, significantly reduced the amplitude of the electrical activity as observed in R wave changes of the surface electrocardiogram recording. In another series of experiments the action of TXB2 on rat heart sarcolemmal ATPase activity was studied. TXB2 significantly reduced the activity of the MG++ dependent - Na+ - K+ stimulated ATPase (Na+ - K+ ATPase) in these membrane preparations in concentrations from 10 ng/ml to 1 microgram/ml. Kinetic studies demonstrated that TXB2 reduced Vmax and increased the concentration required of ATP, Na+ and K+ for half-maximal enzyme activity. TXB2 did not inhibit either Ca++ or ouabain-induced depression of Na+ - K+ ATPase activity. The activity of either Mg++ or Ca++ - stimulated ATPase was not affected by TXB2. These results suggest possible important actions of TXB2 on rat heart activity which may be related to Na+ - K+ ATPase inhibition.