CHARACTERIZATION OF BRADYKININ RECEPTORS FROM JUVENILE PIG CORONARY-ARTERY

Coronary artery rings from juvenile male farm pigs were incubated for 6 h and precontracted with U46619. The rings relaxed in response to de s-Arg(9)-bradykinin (pD(2), 7.78 +/- 0.13; E(max), 87.4 +/- 4.3%) and to bradykinin (pD(2), 8.69 +/- 0.30; E(max), 104.2 +/- 4.4%). These re sponses were abolished by endothelium removal and unaffected by indome thacin whilst NG-nitro-L-arginine reduced the relaxation due to des-Ar g(9)-bradykinin only. Preincubation with cycloheximide or actinomycin had no effect against relaxations mediated by kinins whilst the protei n trafficking inhibitor, brefeldin A, reduced by 52% the maximum respo nse to des-Arg(9)-bradykinin The bradykinin receptor antagonists, des- Arg(9)-[Leu(8)]bradykinin, Hoe 140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), O ic(8)]bradykinin) and NPC 567 (o-Arg-[Hyp(3),D-Phe(7)]bradykinin) anta gonized competitively the response to des-Arg(9)-bradykinin, giving re spective pA(2) values of 6.82 +/- 0.34, 6.63 +/- 0.28 and 6.48 +/- 0.4 1 whereas the non-peptide bradykinin B-2 receptor antagonist, WIN 6433 8 (phosphonium, yclohexylamino)methylene]-amino]-3-(2-naphtalenyl) 1- oxopropyl]amino]-phenyl]-methyl]tributyl chloride, monohydrochloride), was inactive. Hoe 140 and WIN 64338 but not des-Arg(9)[Leu(8)]bradyki nin behaved as competitive antagonists towards the relaxation due to b radykinin. In conclusion, both bradykinin B-2 and B-1 receptors are pr esent on the endothelium of large coronary arteries from juvenile pig. The bradykinin B-1 receptor subtype appears partly inducible and is c oupled to the synthesis of nitric oxide.