Characterization of dextran sulfate-induced guinea pig tracheal plasma extravasation.
We examined the effect of dextran sulfate on guinea pig tracheal vascular permeability. I.v. injection of dextran sulfate (10-100 mg/kg) with captopril (1 mg/kg) induced guinea pig tracheal plasma extravasation. The i.v. administration of bradykinin (0.8-8 micrograms/kg) with captopril (1 mg/kg) also induced plasma extravasation. Bradykinin B2 antagonists, D-Arg[Hyp3-Thi5-D-Tic7-Tic8]-bradykinin (NPC 16731) and D-Arg[Hyp3-Thi5-D-Tic7-Oic8]-bradykinin (Hoe 140), reduced both dextran sulfate (32 mg/kg)- and bradykinin (2.5 micrograms/kg)-induced tracheal plasma extravasation in a dose-dependent manner. However, a cyclooxygenase inhibitor, indomethacin (1 mg/kg), and a neurokinin antagonist, [N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-a llo-threonyl]-L-asparaginyl]-L-serine-D-lactone] (FK 224) (1 mg/kg), had no effect on tracheal plasma extravasation induced by dextran sulfate and bradykinin. Dextran sulfate (32 mg/kg) with captopril (1 mg/kg) greatly increased the bradykinin level in guinea pig plasma. This evidence suggests that dextran sulfate releases bradykinin in guinea pig plasma and causes guinea pig tracheal plasma extravasation via the activation of bradykinin B2-receptors.
Morimoto
H
H
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Yamashita
M
M
Matsuda
A
A
Ohori
M
M
Miyake
H
H
Fujii
T
T
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003911:Dextrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000187:drug effects*
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D003911:Dextrans; D010456:Peptides, Cyclic; C075570:FK 224; C065679:icatibant; D001920:Bradykinin; D007213:Indomethacin