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 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.
Ebara
T
T
Department of Pharmacology, Osaka City University Medical School, Japan.
Miura
K
K
Matsuura
T
T
Imanishi
M
M
Yamano
Y
Y
Kim
S
S
Iwao
H
H
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000503:physiopathology*; D044005:Tetrahydroisoquinolines
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D007546:Isoquinolines; D010972:Platelet Activating Factor; D011453:Prostaglandins; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C056566:S 145; C067430:TCV 309; D007052:Ibuprofen