De Kimpe S J, Tielemans W, Van Heuven-Nolsen D, Nijkamp F P
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, Netherlands.
Eur J Pharmacol. 1994 Aug 11;261(1-2):111-20. doi: 10.1016/0014-2999(94)90308-5.
Bovine isolated mesenteric arterial rings were preincubated for 20 h with interferon-gamma (100 U ml-1) and relaxation in response to bradykinin (10(-12) to 3 x 10(-8) M) was then measured isometrically in an organ bath. Interferon-gamma pretreatment for 20 h markedly attenuated the endothelium-dependent bradykinin relaxation in arteries precontracted with 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619), and the relaxation was reversed to contraction at the highest bradykinin concentrations (-72 +/- 5% for control vs. + 6 +/- 10% for interferon-gamma). Cycloheximide (20 micrograms ml-1) present during the 20-h preincubation completely prevented the interferon-gamma effect. Methyl-L-arginine (1 mM) treatment during the 20-h preincubation also inhibited the interferon-gamma effect on bradykinin relaxation (-47 +/- 18% for interferon-gamma and methyl-L-arginine), which suggests involvement of nitric oxide during the 20-h preincubation with interferon-gamma. In control arteries, des-Arg9-bradykinin, a bradykinin B1 receptor agonist, evoked contractions, which were augmented in rings preincubated for 20 h with interferon-gamma. The bradykinin B1 receptor antagonist, des-Arg9-Leu8-bradykinin (2 microM), present in the organ bath in combination with methyl-L-arginine (1 mM) only present during the 20-h preincubation with interferon-gamma completely restored the bradykinin relaxation (-79 +/- 12%). We suggest two mechanisms. Firstly, prolonged nitric oxide release induced by interferon-gamma during the 20-h preincubation may inhibit bradykinin stimulated endothelium-derived nitric oxide release and action. Secondly, interferon-gamma caused upregulation of the bradykinin B1 receptor-mediated contraction, which may contribute to the decrease in bradykinin-induced vasodilation and cause a reversal to contraction.
将牛肠系膜动脉环与γ-干扰素（100 U/ml）预孵育20小时，然后在器官浴槽中以等长方式测量其对缓激肽（10⁻¹²至3×10⁻⁸ M）的舒张反应。γ-干扰素预处理20小时显著减弱了用9,11-二脱氧-11α,9α-环氧甲撑前列腺素F2α（U46619）预收缩的动脉中内皮依赖性缓激肽舒张反应，并且在最高缓激肽浓度下舒张反应转变为收缩（对照为-72±5%，γ-干扰素处理为+6±10%）。在20小时预孵育期间存在的环己酰亚胺（20μg/ml）完全阻止了γ-干扰素的作用。在20小时预孵育期间用甲基-L-精氨酸（1 mM）处理也抑制了γ-干扰素对缓激肽舒张的作用（γ-干扰素和甲基-L-精氨酸处理为-47±18%），这表明在与γ-干扰素预孵育20小时期间一氧化氮参与其中。在对照动脉中，缓激肽B1受体激动剂去-Arg⁹-缓激肽可引起收缩，在用γ-干扰素预孵育20小时的动脉环中收缩增强。器官浴槽中存在的缓激肽B1受体拮抗剂去-Arg⁹-Leu⁸-缓激肽（2μM）与仅在与γ-干扰素预孵育20小时期间存在的甲基-L-精氨酸（1 mM）联合使用可完全恢复缓激肽舒张反应（-79±12%）。我们提出两种机制。首先，γ-干扰素在20小时预孵育期间诱导的一氧化氮持续释放可能抑制缓激肽刺激的内皮源性一氧化氮释放和作用。其次，γ-干扰素导致缓激肽B1受体介导的收缩上调，这可能导致缓激肽诱导的血管舒张减少并导致收缩逆转。
