Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle.
Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle.
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一氧化氮和前列腺素在人类骨骼肌中的贡献的激动剂依赖性变异性。
DOI：
10.1152/japplphysiol.00966.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Joyner,MichaelJ
中科院分区：
文献类型：
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作者：
Schrage,WilliamG;Dietz,NikiM;Eisenach,JohnH;Joyner,MichaelJ
内皮依赖性扩张剂[一氧化氮（NO）、前列腺素（pg）和内皮衍生超极化因子（EDHF）]在人体四肢中的相对作用尚不清楚。我们检验了内皮激动剂乙酰胆碱（ACh； 1、2和4 μg·dl - 1·min - 1）和缓激素（BK； 6.25、25和50 ng·dl - 1·min - 1）对NO和pg的相对贡献的假设。我们用静脉闭塞容积描记术测量了50名健康志愿者（27±1年）在没有和存在NO合成酶抑制剂的情况下肱动脉输注ACh或BK的前臂血流（FBF）。与ng -单甲基-l-精氨酸（l-NMMA）]和环加氧酶（COX；与酮咯酸）。此外，在动物实验中，我们验证了NOS + cox非依赖性扩张（在fl- nmma +酮咯酸存在的情况下，可能是EDHF）可以被外源性NO给药抑制的观点。在ACh对照组中，FBF增加了约10倍；l-NMMA降低了基线FBF和乙酰胆酸扩张，而添加酮罗拉酸没有进一步的影响。单独使用酮咯酸不改变乙酰胆碱的扩张，但添加l- nmma可显著降低乙酰胆碱的扩张。对于BK输注，FBF在对照条件下增加了~ 10倍；l-NMMA有降低BK扩张的趋势（P< 0.1），添加酮洛酸可显著降低BK扩张。与乙酰胆酸类似，单独使用酮咯酸不会改变BK扩张，但添加l- nmma会降低BK扩张。为了验证NO可以抑制不依赖NOS + cox的扩张部分，我们在ACh或BK期间注入一定剂量的硝普钠（NO-clamp技术），以恢复因toli - nmma导致的基线血流量减少。无论治疗顺序如何，NO钳钳恢复了基线FBF，但没有减少对ACh或BK的NOS + cox不依赖的扩张。我们得出结论，在健康年轻人中，ACh更依赖于NO，而BK主要依赖于NOS + cox不依赖机制（EDHF）， NO和pg的贡献在ACh和BK之间是不同的。在人类前臂中，NOS + cox不依赖的扩张对NO的反馈抑制不敏感。
The relative contributions of endothelium-dependent dilators [nitric oxide (NO), prostaglandins (PGs), and endothelium-derived hyperpolarizing factor (EDHF)] in human limbs are poorly understood. We tested the hypothesis that relative contributions of NO and PGs differ between endothelial agonists acetylcholine (ACh; 1, 2, and 4 μg·dl−1·min−1) and bradykinin (BK; 6.25, 25, and 50 ng·dl−1·min−1). We measured forearm blood flow (FBF) using venous occlusion plethysmography in 50 healthy volunteers (27 ± 1 yr) in response to brachial artery infusion of ACh or BK in the absence and presence of inhibitors of NO synthase [NOS; withNG-monomethyl-l-arginine (l-NMMA)] and cyclooxygenase (COX; with ketorolac). Furthermore, we tested the idea that the NOS + COX-independent dilation (in the presence ofl-NMMA + ketorolac, presumably EDHF) could be inhibited by exogenous NO administration, as reported in animal studies. FBF increased ∼10-fold in the ACh control;l-NMMA reduced baseline FBF and ACh dilation, whereas addition of ketorolac had no further effect. Ketorolac alone did not alter ACh dilation, but addition ofl-NMMA reduced ACh dilation significantly. For BK infusion, FBF increased ∼10-fold in the control condition;l-NMMA tended to reduce BK dilation (P< 0.1), and addition of ketorolac significantly reduced BK dilation. Similar to ACh, ketorolac alone did not alter BK dilation, but addition ofl-NMMA reduced BK dilation. To test the idea that NO can inhibit the NOS + COX-independent portion of dilation, we infused a dose of sodium nitroprusside (NO-clamp technique) during ACh or BK that restored the reduction in baseline blood flow due tol-NMMA. Regardless of treatment order, the NO clamp restored baseline FBF but did not reduce the NOS + COX-independent dilation to ACh or BK. We conclude that the contribution of NO and PGs differs between ACh and BK, with ACh being more dependent on NO and BK being mostly dependent on a NOS + COX-independent mechanism (EDHF) in healthy young adults. The NOS + COX-independent dilation does not appear sensitive to feedback inhibition from NO in the human forearm.