ROLE OF PLATELET-ACTIVATING-FACTOR AND PROSTANOIDS IN HEMODYNAMIC-CHANGES IN RAT EXPERIMENTAL ENDOTOXIC-SHOCK

The present experiments were conducted to elucidate the role of platel et-activating factor (PAF) and cyclooxygenase products in the cardiova scular responses to endotoxin in anesthetized rats. Endotoxin (10 mg/k g, i.v.) induced hypotension that was accompanied by a decrease in car diac output and an increase in calculated total peripheral resistance, suggesting that this hypotension mainly resulted from the reduced car diac output. The endotoxin-induced decrease in cardiac output and hemo concentration was significantly attenuated by TCV-309 (a PAF receptor antagonist), ibuprofen (a cyclooxygenase inhibitor) or S-1452 (a throm boxane A(2)/prostaglandin H-2-receptor antagonist). During the 3-hr ob servation period following endotoxin administration, ibuprofen and S-1 452 showed only early protection and TCV-309 showed late attenuation o f the endotoxin-induced hypotension. Tachycardiac responses to endotox in were only blocked by ibuprofen but not by TCV-309 or S-1452. These results suggest that both PAF and cyclooxygenase product(s), including thromboxane A(2), mediate the decrease in cardiac output and hypotens ion in rat experimental endotoxic shock. Cyclooxygenase product(s) oth er than thromboxane A(2) or prostaglandin endoperoxide may be involved in the endotoxin-induced increase in heart rate.