Inhibition of endothelium-dependent vasodilation by Escherichia coli endotoxemia.
Inhibition of endothelium-dependent vasodilation by Escherichia coli endotoxemia.
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大肠杆菌内毒素血症抑制内皮依赖性血管舒张。
DOI：
10.1097/00024382-199412000-00011
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Adams,HR
中科院分区：
文献类型：
--
作者：
Parker,JL;Myers,PR;Zhong,Q;Kim,K;Adams,HR
为了检验这一假设，即内皮衍生的舒张因子/一氧化氮的释放被抑制革兰氏阴性脂多糖（LPS;内毒素），我们研究了内皮非依赖性和内皮依赖性血管扩张剂在主动脉血管平滑肌分离豚鼠注射生理盐水（对照）或诱导大肠杆菌内毒素血症后4小时。LPS显著抑制内皮依赖性激动剂乙酰胆碱（ACh; 10 10-10 5 M）和ADP（10 8-10 5 M）的扩血管反应。然而，LPS并不影响血管舒张反应的非内皮依赖性激动剂硝普钠（10 10-10 4 M）。一氧化氮合酶（NOS）抑制剂N [γ]-硝基-L-精氨酸甲酯（L-NAME）抑制ACh的血管舒张反应;而环氧合酶抑制剂吲哚美辛（INDO）并不减少ACh的血管舒张作用。L-NAME和INDO均不影响硝普钠对LPS或对照血管的舒张作用。与此相反，L-NAME转换ADP的血管舒张作用的血管收缩反应，分别被阻断的INDO和血栓烷合酶抑制剂dazoxiben，这表明ADP释放NO，也血管收缩剂和血小板聚集类花生烷血栓烷A2。这些结果表明，急性（4小时）内毒素血症抑制血管内皮细胞中的NOS组成型亚型的功能。由于L-NAME揭示了内源性嘌呤受体激动剂ADP的血管收缩作用，抑制NOS的药理学药物可能会加剧LPS诱导的内皮NOS抑制;这一系列事件可能导致血管扩张储备减少，并可能导致革兰氏阴性脓毒症期间血小板聚集增加。
To test the hypothesis that release of endothelium-derived relaxing factor/nitric oxide is inhibited by Gram-negative lipopolysaccharide (LPS; endotoxin), we examined endothelium-independent and endothelium-dependent vasodilator agents in aortic vascular smooth muscle isolated from guinea pigs 4 h after injection of saline (controls) or induction of Escherichia coli endotoxemia. LPS significantly inhibited vasodilator responses to the endothelium-dependent agonists acetylcholine (ACh; 10 10-10 5M) and ADP (10 8-10 5M). However, LPS did not affect vasodilator responses to the endothelium-independent agonist nitroprusside (10 10-10 4M). The nitric oxide synthase (NOS) inhibitor N [gamma]-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to ACh; whereas, the cyclooxygenase inhibitor indomethacin (INDO) did not reduce vasodilator effects of ACh. Neither L-NAME nor INDO affected the vasodilator effects of nitroprusside in LPS or control vessels. In contrast, L-NAME converted the vasodilator action of ADP to a vasoconstrictor response that was blocked individually by INDO and the thromboxane synthase inhibitor dazoxiben, suggesting that ADP releases NO and also the vasoconstrictor and platelet aggregating eicosanoid thromboxane A2. These findings suggest that acute (4 h) endotoxemia inhibits function of the constitutive isoform of NOS in vascular endothelial cells. Since L-NAME unmasked a vasoconstrictor action of the endogenous purinoceptor agonist ADP, pharmacologic agents that inhibit NOS may exacerbate LPS-induced inhibition of endothelial NOS; this series of events could lead to diminution of vasodilator reserves and perhaps to augmentation of platelet aggregation during Gram-negative sepsis.