Captopril uncovers kinin-dependent release of arachidonic acid metabolites in carrageenin-induced rat pleurisy.
As previously reported, pretreatment with captopril significantly enhanced pleural exudation of rat carrageenin-induced pleurisy. However, in high molecular weight kininogen-deficient rats (B/N-Katholiek), the pleural exudate volume was significantly less than that of the normal strain (B/N-Kitasato), and captopril pretreatment did not enhance exudation. In the present study, the following additional evidences were demonstrated: 1) Captopril did not increase 6-keto-PGF1 alpha level in the deficient strain, but it was significantly increased in the normal strain after captopril treatment; 2) simultaneous administration of soybean trypsin inhibitor with carrageenin markedly suppressed the exudate volume and levels of 6-keto-PGF1 alpha in the normal strain; and 3) indomethacin also suppressed pleural fluid accumulation and the production of arachidonate metabolites. These data suggest that carrageenin causes intrinsic kinin-release through the activation of plasma kallikrein and then in turn, the kinin stimulates the production of arachidonic acid metabolites. Thus these products and kinin may interact to induce more plasma exudation in carrageenin inflammation. The results also indicate that captopril uncovers the effects of bradykinin on exudation and stimulation of arachidonate metabolite production; otherwise, the biological effect of kinin is too slight to produce a clear effect at the initial phase of the inflammation.
Dozen
M
M
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Yamaki
K
K
Oh-Ishi
S
S
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D002351:Carrageenan; D007213:Indomethacin / Q000494:pharmacology; D007704:Kininogens / Q000172:deficiency; D007705:Kinins / Q000502:physiology*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology
D001095:Arachidonic Acids; D007704:Kininogens; D007705:Kinins; D002351:Carrageenan; D014360:Trypsin Inhibitor, Kunitz Soybean; D002216:Captopril; D007213:Indomethacin