Role of Platelet-Activating Factor and Prostanoids in Hemodynamic Changes in Rat Experimental Endotoxic Shock

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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 A<SUB>2</SUB>/prostaglandin H<SUB>2</SUB>-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 A<SUB>2</SUB>, mediate the decrease in cardiac output and hypotension in rat experimental endotoxic shock. Cyclooxygenase product(s) other than thromboxane A<SUB>2</SUB> or prostaglandin endoperoxide may be involved in the endotoxin-induced increase in heart rate.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 71(3), 247-253, 1996-07

    The Japanese Pharmacological Society

References:  29

Cited by:  1


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