Role of synergistic action of PAF and kinin in bacterial endotoxin-induced hypotension in rats.
Involvement of PAF and kinin in the endotoxin (LPS)-induced hypotension was examined in the rat strains, Brown Norway (B/N);Kitasato (Normal) and B/N-Kitasato rats, intravenous injection of 10 mg/kg LPS caused a hypotension composed on two phases (15 min and 70 min after LPS injection). However in the kininogen-deficient B/N-Katholiek rats. LPS induced only the second phase. Pretreatment with bradykinin (BK) antagonist. Hoe 140 suppressed LPS-induced hypotension of normal rats to the level of Katholiek rats. TCV 309, a PAF-antagonist, suppressed the LPS-hypotension almost completely in the both strains. The reason why the PAF-antagonist showed almost complete inhibition, could be explained by a synergism. Because concomitant injection of a small amount of BK with PAF caused potentiation of the effect of the PAF action. These results suggest that formation of endogenous BK contributes mainly to the 1st phase of LPS-hypotension, and PAF contributes to both phases, by either direct and synergistic actions.
Oh-Ishi
S
S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Ishida
H
H
Ueno
A
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007704:Kininogens / Q000172:deficiency; D007705:Kinins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007704:Kininogens; D007705:Kinins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D003907:Dexamethasone; D001920:Bradykinin; D007213:Indomethacin