Churchill L, Ward P E
Hypertension. 1987 Jun;9(6 Pt 2):III1-5. doi: 10.1161/01.hyp.9.6_pt_2.iii1.
We have previously reported that des-Arg9-bradykinin can relax the phenylephrine-precontracted rabbit mesenteric artery through B1 kinin receptor stimulation and the subsequent release of prostaglandins. In the present study, we have found that this relaxant response can be converted to a contractile response by the cyclooxygenase inhibitor indomethacin. Contraction was dose-dependent and was blocked by the B1 receptor antagonist [Leu8]des-Arg9-bradykinin, with a pA2 value obtained by Schild regression similar to that reported for relaxation in the absence of indomethacin. Des-Arg10-kallidin (ED50 = 5.0 +/- 0.9 X 10(-9) M) was 16 times more potent than des-Arg9-bradykinin (ED50 = 8.1 +/- 0.8 X 10(-8) M) in contracting the indomethacin-treated artery and was also blocked by [Leu8]des-Arg9-bradykinin. In contrast, only 13 out of 24 indomethacin-treated vessels contracted in response to bradykinin, which had only one tenth and one 160th the potency (ED50 = 9.9 +/- 1.8 X 10(-7) M) of des-Arg9-bradykinin and des-Arg10-kallidin, respectively. B1 kinin receptor-mediated contraction in the presence of indomethacin was unaffected by the dual cyclooxygenase-lipoxygenase inhibitor BW 755c. These results indicate that des-Arg-kinins can stimulate both relaxation and contraction of the phenylephrine-precontracted rabbit mesenteric artery through stimulation of B1 kinin receptors. The relaxation is dependent on the release of prostaglandins, while the contraction may represent a direct effect.
我们之前曾报道，去精氨酸9-缓激肽可通过刺激B1激肽受体并随后释放前列腺素，使苯肾上腺素预收缩的兔肠系膜动脉舒张。在本研究中，我们发现这种舒张反应可被环氧化酶抑制剂吲哚美辛转化为收缩反应。收缩呈剂量依赖性，并被B1受体拮抗剂[亮氨酸8]去精氨酸9-缓激肽阻断，通过Schild回归得到的pA2值与在无吲哚美辛情况下报道的舒张pA2值相似。去精氨酸10-胰激肽（ED50 = 5.0 +/- 0.9×10^(-9) M）在收缩经吲哚美辛处理的动脉方面比去精氨酸9-缓激肽（ED50 = 8.1 +/- 0.8×10^(-8) M）强16倍，并且也被[亮氨酸8]去精氨酸9-缓激肽阻断。相比之下，在24条经吲哚美辛处理的血管中，只有13条对缓激肽产生收缩反应，缓激肽的效力分别仅为去精氨酸9-缓激肽和去精氨酸10-胰激肽的十分之一和一百六十分之一（ED50 = 9.9 +/- 1.8×10^(-7) M）。在存在吲哚美辛的情况下，B1激肽受体介导的收缩不受双环氧化酶-脂氧合酶抑制剂BW 755c的影响。这些结果表明，去精氨酸激肽可通过刺激B1激肽受体，刺激苯肾上腺素预收缩的兔肠系膜动脉的舒张和收缩。舒张依赖于前列腺素的释放，而收缩可能代表直接作用。
