Evidence that an l‐arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin
Evidence that an l‐arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin
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有证据表明，L-精氨酸/一氧化氮依赖性组织环鸟苷酸含量升高与内毒素抑制血管反应性有关
DOI：
10.1111/j.1476-5381.1991.tb12298.x
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发表时间：
1991
影响因子：
7.3
通讯作者：
J. Stoclet
中科院分区：
文献类型：
--
作者：
I. Fleming;G. Julou‐Schaeffer;G. Gray;J. Parratt;J. Stoclet
1本研究的目的是研究大鼠腹腔注射细菌内毒素（E.coli.）4 h后主动脉环收缩反应性、L‐精氨酸途径激活和组织中3′：5′-环磷酸鸟苷（cyclicGMP）水平之间的关系。脂多糖，LPS，20 mg kg−1）。2 LPS处理导致对去甲肾上腺素（NA）的敏感性和最大收缩反应降低。3最大收缩反应的抑制被6-anilo-5，8-quinolinedione（LY 83583，10 μm）恢复到对照组，其阻止可溶性鸟苷酸环化酶的激活。4 LPS处理大鼠组织中的环GMP水平是对照（盐水处理）大鼠组织中检测到的环GMP水平的2倍。在存在和不存在功能性内皮的情况下均观察到LPS诱导的环GMP含量增加。5向最大收缩的主动脉环中加入l-精氨酸（1 mm）可使LPS处理大鼠的主动脉环显著舒张，但对照动物的主动脉环则无显著舒张。在LPS处理组中，添加l-精氨酸也与环GMP含量的显著增加相关。l-精氨酸对对照环的环GMP含量没有影响。d-精氨酸（1 mm）无影响。6在LPS处理的大鼠环中，NG-硝基-l-精氨酸甲酯（l-NAME，300 μm）是一种一氧化氮（NO）产生的抑制剂，可增加对NA的收缩反应，并阻止LPS诱导的环GMP含量增加。在对照环中，l-NAME仅在内皮保持完整时增加NA敏感性，并将这些环的环GMP含量降低至对照内皮剥脱环的含量。7这些结果表明，LPS诱导的对NA的低反应性继发于血管组织中L-精氨酸途径的激活和随后可溶性鸟苷酸环化酶的激活。此外，他们表明LPS诱导非内皮细胞中NO样松弛因子的产生。
1 The aim of this investigation was to study the relationship between contractile responsiveness, activation of the l‐arginine pathway and tissue levels of guanosine 3′:5′‐cyclic monophosphate (cylic GMP) in aortic rings removed from rats 4 h after intraperitoneal administration of bacterial endotoxin (E.coli. lipopolysaccharide, LPS, 20 mg kg−1). 2 LPS‐treatment resulted in a reduction of the sensitivity and maximal contractile response to noradrenaline (NA). 3 Depression of the maximal contractile response was restored to control by 6‐anilo‐5,8‐quinolinedione (LY 83583, 10 μm), which prevents activation of soluble guanylate cyclase. 4 Cyclic GMP levels in tissue from LPS‐treated rats were 2 fold greater than cyclic GMP levels detected in tissue from control (saline‐treated) rats. The LPS‐induced increase in cyclic GMP content was observed both in the presence and absence of functional endothelium. 5 Addition of l‐arginine (1 mm) to maximally contracted aortic rings produced significant relaxation of rings from LPS‐treated rats but not rings from control animals. In the LPS‐treated group, addition of l‐arginine was also associated with a significant increase in cyclic GMP content. l‐Arginine had no effect on the cyclic GMP content of control rings. d‐Arginine (1 mm) was without effect. 6 In rings from LPS‐treated rats, NG‐nitro‐l‐arginine methyl ester (l‐NAME, 300 μm) an inhibitor of nitric oxide (NO) production, increased the contractile response to NA and prevented the LPS‐induced increase in cyclic GMP content. In control rings, l‐NAME increased the NA sensitivity only when the endothelium remained intact and reduced the cyclic GMP content of these rings to that of control endothelium‐denuded rings. 7 These results demonstrate that LPS‐induced hyporeactivity to NA occurs secondarily to activation of the l‐arginine pathway and subsequent activation of soluble guanylate cyclase in vascular tissue. In addition they suggest that LPS induces the production of an NO‐like relaxing factor in non‐endothelial cells.
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DOI：
10.1016/0006-291x(89)92615-6
发表时间：
1989-06
影响因子：
3.1
作者：
D. Stuehr;Nyoun Soo Kwon;Steven S. Gross;Bonnie A. Thiel;Roberto Levi;Carl Nathan
通讯作者：
D. Stuehr;Nyoun Soo Kwon;Steven S. Gross;Bonnie A. Thiel;Roberto Levi;Carl Nathan
血管平滑肌源性松弛因子（MDRF）及其与一氧化氮的密切相似性。
DOI：
10.1016/0006-291x(90)91243-l
发表时间：
1990
影响因子：
3.1
作者：
Wood,KS;Buga,GM;Byrns,RE;Ignarro,LJ
通讯作者：
Ignarro,LJ
影响因子：
2.9
作者：
MARLETTA, MA;YOON, PS;WISHNOK, JS
通讯作者：
WISHNOK, JS
DOI：
10.1073/pnas.85.22.8664
发表时间：
1988-11-01
影响因子：
11.1
作者：
SAKUMA, I;STUEHR, DJ;LEVI, R
通讯作者：
LEVI, R