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硝酸甘油中间供体和血管扩张效应有关吗？
Andrei L. Kleschyov, Matthias Oelze,et al. Does Nitric Oxide Mediate the Vasodilator Activity of nitroglycerin?[J]，Circulation Research，2003年93卷9期
nitroglycerin (glyceryl trinitrate, GTN) relaxes blood vessels primarily via activation of the soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK-I) pathway. Although the precise mechanism of sGC activation by GTN in the vascular wall is unknown, the mediatory role of nitric oxide (NO) has been postulated. We tested the GTN/NO hypothesis in different types of isolated rat and rabbit blood vessels using two novel approaches: (1) EPR spin trapping using colloid Fe(DETC)2 and (2) analysis of cGK-I–dependentphosphorylation of the vasodilator-stimulated phosphoprotein at Ser239 (P-VASP). For comparison, another organic nitrate, isosorbide dinitrate (ISDN), and endothelium-dependent vasodilator, calcium ionophore A23187, were tested. We found a marked discrepancy between GTN’s strong vasoactivity (vasodilation and augmentation of P-VASP) and its poor NO donor properties. In aortas precontracted with phenylephrine, GTN, ISDN, and A23187 induced nearly full relaxations (>80%) and doubling of vascular P-VASP content at concentrations of 100 nmol/L, 100 μmol/L, and 1 μmol/L, respectively. GTN applied in vasorelaxant concentrations (10 to 1000 nmol/L) did not significantly increase the basal vascular NO production, in contrast to ISDN and A23187. The absence of GTN-derived NO was confirmed in rabbit vena cava and renal artery. A significant increase in vascular NO formation was observed only at suprapharmacological GTN concentrations (>10 μmol/L). The concentration dependency of NO formation from GTN was comparable to that of ISDN, although the latter exhibits 100-folds lower vasorelaxant potency. We conclude that GTN activates the sGC/cGMP/cGK-I pathway and induces vasorelaxation without intermediacy of the free radical NO.
硝酸甘油中间供体和血管扩张效应有关吗？
Andrei L. Kleschyov, Matthias Oelze,et al. Does Nitric Oxide Mediate the Vasodilator Activity of nitroglycerin?[J]，Circulation Research，2003年93卷9期
硝酸甘油扩血管效应主要通过激活可溶性鸟苷酸环化酶(sGC)/cGMP/cGMP依赖的蛋白激酶(cGK-I)通路。虽然精确的硝酸甘油激活sGC的机制还不清楚，NO的媒介作用已经被证实。我们应用两种新的方法检验NTG/NO理论在不同类型的单独大鼠和兔子血管上，1运用胶体铁电子顺磁共振旋转诱捕，2 分析cGK-I–依赖的Ser239(P-VASP) 血管扩张磷酸蛋白刺激的磷酸化。为了对比，另一种硝基化合物; 二硝基异山梨醇（ISDN）；内皮依赖血管扩张剂：该离子载体A23187座对比。我们发现一种矛盾现象：NTG具有强大的血管活性却拥有小的NO供体效应。在大动脉本肾上腺素与处理后，NTG，ISDN，A23187诱导完全扩张。分别运用100 nmol/L, 100 μmol/L, and 1 μmol/L,来检测P-VASP的浓度。NTG与ISDN，A23187相比没有明显的NO产物升高效应。硝酸甘油源的NO被兔腔静脉和肾动脉实验证实。只有在>10 μmol/L的NTG才发现具有NO升高效应。我们得出结论：硝酸甘油激活sGC/cGMP/cGK-I通路和诱导血管扩张与NO中间体无关。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-02-24 05:11
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