Add time:08/25/2019         Source:sciencedirect.com

Coronary artery rings from juvenile male farm pigs were incubated for 6 h and precontracted with U46619. The rings relaxed in response to des-Arg9-bradykinin (pD2, 7.78 ± 0.13; Emax, 87.4 ± 4.3%) and to bradykinin (pD2, 8.69 ± 0.30; Emax, 104.2 ± 4.4%). These responses were abolished by endothelium removal and unaffected by indomethacin whilst NG-nitro-l-arginine reduced the relaxation due to des-Arg9-bradykinin only. Preincubation with cycloheximide or actinomycin had no effect against relaxations mediated by kinins whilst the protein trafficking inhibitor, brefeldin A, reduced by 52% the maximum response to des-Arg9-bradykinin. The bradykinin receptor antagonists, des-Arg9-[Leu8]bradykinin, Hoe 140 (d-Arg-[Hyp3, Thi5, d-Tic7,Oic8]bradykinin) and NPC 567 (d-Arg-[Hyp3,d-Phe7]bradykinin) antagonized competitively the response to des-Arg9-bradykinin, giving respective pA2 values of 6.82 ± 0.34, 6.63 ± 0.28 and 6.48 ± 0.41 whereas the non-peptide bradykinin B2 receptor antagonist, WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]-3-(2-naphtalenyl) 1-oxopropyl]amino]-phenyl]-methyl]tributyl chloride, monohydrochloride), was inactive. Hoe 140 and WIN 64338 but not des-Arg9[Leu8]bradykinin behaved as competitive antagonists towards the relaxation due to bradykinin. In conclusion, both bradykinin B2 and B1 receptors are present on the endothelium of large coronary arteries from juvenile pig. The bradykinin B1 receptor subtype appears partly inducible and is coupled to the synthesis of nitric oxide.

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