Tetrahydrobiopterin, a cofactor for nitric oxide synthase, produces endothelium-dependent dilation of mouse pial arterioles.
Tetrahydrobiopterin, a cofactor for nitric oxide synthase, produces endothelium-dependent dilation of mouse pial arterioles.
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四氢生物蝶呤是一氧化氮合酶的辅助因子，可产生小鼠软脑膜小动脉的内皮依赖性扩张。
DOI：
10.1161/01.str.28.1.186
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发表时间：
1997
期刊：
影响因子：
8.3
通讯作者：
Rosenblum,WI
中科院分区：
文献类型：
--
作者：
Rosenblum,WI
背景与目的四氢生物蝶呤(THBP)是一氧化氮合酶(NOS)的重要辅因子，参与合成内皮衍生的松弛因子(EDRF)，介导乙酰胆碱(ACh)的血管松弛作用。以往的研究表明，EDRFACH是由小鼠软脑膜小动脉内皮细胞持续合成和释放的。如果是这样的话，人们可以预测，THBP的加入将增加局部EDRFA的产生，并产生一种内皮依赖性的松弛，这种松弛可以被一种已知的NOS抑制剂所阻断。本研究验证了这一预测。方法通过活体电视显微镜对持续充血的开颅手术部位的软脑膜血管进行观察。观察内皮损伤前后及一氧化氮合酶抑制剂L单甲基精氨酸局部治疗前后血管直径的变化。结果10−3和10−2mol/L THBP对血管内皮细胞有剂量依赖性的松弛作用。这种反应几乎被内皮损伤所消除。LNMMA 10THBP 6mol/L对血管扩张也有明显的抑制作用。结论上述数据与文献报道的−是内皮型一氧化氮合酶的辅因子一致。这些数据与先前的结果一致，表明EDRFAChs是不断合成和释放的。THBP似乎增加了这种合成，从而增加了EDRFACh的局部释放水平。根据其他研究，EDRFAChs的持续自发合成/释放可调节基础张力，并有助于维持无血小板的内皮表面。
Background and PurposeTetrahydrobiopterin (THBP) is an essential cofactor for nitric oxide synthase (NOS), which is responsible for the synthesis of the endothelium-derived relaxing factor (EDRF) responsible for mediating the vasorelaxation produced by acetylcholine (ACh). Previous publications suggest that EDRFAChis continuously synthesized and released from the endothelium of mouse pial arterioles. If so, then one may predict that addition of THBP will increase the local production of EDRFAChand produce an endothelium-dependent relaxation that can be blocked by application of a known inhibitor of NOS. This study tests the prediction.MethodsThe pial vessels were observed at a continuously suffused craniotomy site by means of intravital television microscopy. The effects of topically applied THBP on diameter were monitored before and after endothelial damage and before and after local treatment with the NOS inhibitorN-guanidino-l-monomethyl arginine (LNMMA). The endothelial damage was produced by a helium-neon laser in the presence of Evans blue dye.ResultsA dose-dependent relaxation was produced by 10−3and 10−2mol/L THBP. The response was virtually eliminated by endothelial injury. LNMMA 10−6mol/L also greatly inhibited dilation.ConclusionsThe data are consistent with all reports that THBP is a cofactor for constitutive endothelial NOS. The data are consonant with previous results suggesting that EDRFAChis continually synthesized and released. It appears that THBP increases this synthesis and consequently the local level of released EDRFACh. The continuous spontaneous synthesis/release of EDRFAChmodulates basal tone and, according to other studies, helps maintain a platelet-free endothelial surface.