Tsuneyuki Ebara (1), Katsuyuki Miura (1,*), Takeshi Matsuura (1), Masahito Imanishi (2), Yoshiki Yamano (3), Shokei Kim (1) and Hiroshi Iwao (1)
(1) Department of Pharmacology and (3) Department of Orthopaedic Surgery, Osaka City University Medical School, Osaka 545, Japan (2) 0saka City General Hospital, Osaka 534, Japan (*) To whom correspondence should be addressed.
Abstract: The present experiments were conducted to elucidate the role of platelet-activating factor (PAF) and cyclooxygenase products in the cardiovascular responses to endotoxin in anesthetized rats. Endotoxin (10 mg/kg, i.v.) induced hypotension that was accompanied by a decrease in cardiac output and an increase in calculated total peripheral resistance, suggesting that this hypotension mainly resulted from the reduced cardiac output. The endotoxin-induced decrease in cardiac output and hemoconcentration was significantly attenuated by TCV-309 (a PAF receptor antagonist), ibuprofen (a cyclooxygenase inhibitor) or S-1452 (a thromboxane A2/prostaglandin H2-receptor antagonist). During the 3-hr observation period following endotoxin administration, ibuprofen and S-1452 showed only early protection and TCV-309 showed late attenuation of the endotoxin-induced hypotension. Tachycardiac responses to endotoxin 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 A2, mediate the decrease in cardiac output and hypotension in rat experimental endotoxic shock. Cyclooxygenase product(s) other than thromboxane A2 or prostaglandin endoperoxide may be involved in the endotoxin-induced increase in heart rate.
Endotoxin, Platelet-activating factor, Cyclooxygenase, Hemodynamics
[Back to TOC]