Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia.
Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia.
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体外灌注主动脉中 EDRF 和 NO 的释放：体内大肠杆菌内毒素血症的抑制。
DOI：
10.1152/ajpheart.1995.268.3.h955
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Parker,JL
中科院分区：
文献类型：
--
作者：
Myers,PR;Zhong,Q;Jones,JJ;Tanner,MA;Adams,HR;Parker,JL
关于内毒素和内皮源性舒张因子（EDRF）之间的相互关系，以往的研究得出了相互矛盾的结果。我们测试了体内内毒素血症抑制基础和/或激动剂介导的EDRF和一氧化氮（NO）释放的假设。在豚鼠主动脉中测定了大肠杆菌内毒素血症（4 mg/kg内毒素i. p.）16 h后EDRF生物活性、NO产生和NO合酶（NOS）活性。在标准等长条件下研究了主动脉环的内皮依赖性舒张。内毒素血症导致灌注主动脉中基础EDRF生物活性降低89%，基础NO产生降低62%。EDRF的生物活性和NO的产生响应于受体依赖性激动剂乙酰胆碱和ADP显着降低灌注主动脉内毒素血症动物。与此相反，内毒素没有显着抑制EDRF的生物活性和NO产生的受体非依赖性激动剂A-23187。内毒素血症动物的主动脉环同样显示对乙酰胆碱和ADP的血管舒张反应降低，但对A-23187无反应。诱导（Ca 2+独立）NOS活性在对照组和内毒素治疗组动物中没有显着差异。这些结果表明，长期内毒素血症导致EDRF释放减少，这与革兰氏阴性脓毒症期间内毒素血症降低基础和激动剂刺激的EDRF生物活性和NO产生以及内皮依赖性血管舒张储备丧失的解释一致。
Previous studies have yielded contradictory results about interrelations between endotoxin and endothelium-derived relaxing factor (EDRF). We tested the hypothesis that in vivo endotoxemia inhibits basal and/or agonist-mediated release of EDRF and nitric oxide (NO). EDRF bioactivity, NO production, and NO synthase (NOS) activity were measured in aorta from guinea pigs following 16 h of Escherichia coli endotoxemia (4 mg/kg endotoxin i.p.). Endothelium-dependent relaxation of aortic rings was studied under standard isometric conditions. Endotoxemia resulted in an 89% reduction in basal EDRF bioactivity and a 62% reduction in basal NO production in perfused aorta. EDRF bioactivity and NO production in response to the receptor-dependent agonists acetylcholine and ADP were significantly reduced in perfused aorta from endotoxemic animals. In contrast, endotoxin did not significantly inhibit EDRF bioactivity and NO production by the receptor-independent agonist A-23187. Aortic rings from endotoxemic animals likewise showed decreased vasodilator responses to acetylcholine and ADP but not to A-23187. Inducible (Ca2+ independent) NOS activity was not significantly different in control and endotoxin-treated animals. These findings indicate that prolonged endotoxemia resulted in diminution of release of EDRF, consistent with the interpretation that endotoxemia decreases basal and agonist-stimulated EDRF bioactivity and NO production with loss of endothelium-dependent vasodilator reserves during gram-negative sepsis.