Pruneau D, Luccarini J M, Defrêne E, Paquet J L, Bélichard P
Centre de Recherche, Laboratoires Fournier S.C.A., Daix, France.
Eur J Pharmacol. 1996 Feb 15;297(1-2):53-60. doi: 10.1016/0014-2999(95)00720-2.
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.
将幼年雄性农场猪的冠状动脉环孵育6小时，并用U46619进行预收缩。这些环对去精氨酸9 - 缓激肽（pD2，7.78±0.13；Emax，87.4±4.3%）和缓激肽（pD2，8.69±0.30；Emax，104.2±4.4%）产生舒张反应。这些反应在内皮去除后消失，且不受吲哚美辛影响，而NG - 硝基 - L - 精氨酸仅降低了去精氨酸9 - 缓激肽引起的舒张。用环己酰亚胺或放线菌素预孵育对缓激肽介导的舒张无影响，而蛋白质转运抑制剂布雷菲德菌素A使去精氨酸9 - 缓激肽的最大反应降低了52%。缓激肽受体拮抗剂去精氨酸9 - [亮氨酸8]缓激肽、Hoe 140（D - 精氨酸 - [Hyp3, Thi5, D - Tic7, Oic8]缓激肽）和NPC 567（D - 精氨酸 - [Hyp3, D - 苯丙氨酸7]缓激肽）竞争性拮抗去精氨酸9 - 缓激肽的反应，其各自的pA2值分别为6.82±0.34、6.63±0.28和6.48±0.41，而非肽类缓激肽B2受体拮抗剂WIN 64338（[[4 - [[2 - [[双（环己基氨基）亚甲基]氨基] - 3 - （2 - 萘基）1 - 氧代丙基]氨基] - 苯基] - 甲基]三丁基氯化铵，盐酸盐）无活性。Hoe 140和WIN 64338对缓激肽引起的舒张表现为竞争性拮抗剂，而去精氨酸9[亮氨酸8]缓激肽则不然。总之，缓激肽B2和B1受体均存在于幼年猪大冠状动脉的内皮上。缓激肽B1受体亚型似乎部分可诱导，且与一氧化氮的合成偶联。
