Use of a nitronyl nitroxide to discriminate the contribution of nitric oxide radical in endothelium-dependent relaxation of control and diabetic blood vessels.
Use of a nitronyl nitroxide to discriminate the contribution of nitric oxide radical in endothelium-dependent relaxation of control and diabetic blood vessels.
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发表时间：
1997-10
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通讯作者：
G. Pieper;W. Siebeneich
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作者：
G. Pieper;W. Siebeneich
硝酰基氮氧化物与一氧化氮自由基（. NO）反应形成亚氨基氮氧化物。我们使用硝酰基氮氧化物[2-（4-羧基苯基）-4，4，5，5-四甲基咪唑啉-1-氧基3氧化物]（CPTIO）来评价NO对对照和糖尿病大鼠主动脉环的基础张力和乙酰胆碱诱导的内皮依赖性舒张的贡献。在用苯妥英钠预收缩的环中，CPTIO产生了额外的张力增加，其在对照组中比糖尿病环中更大。CPTIO后的张力与用NO合酶抑制剂L-硝基精氨酸预处理的环或无内皮的环中观察到的张力相似。这种增加对吲哚美辛、半胱氨酸、四乙基铵或过氧化氢酶不敏感，但对可溶性鸟苷酸环化酶抑制剂1H-[1，2，4]恶二唑并[4，3，-a]喹喔啉-1-酮的抑制敏感。在对照组和糖尿病组，左旋硝基精氨酸分别阻断了100%和90%的ACH舒张。相比之下，CPTIO产生的浓度依赖性抑制ACH诱导的松弛，是更大的控制环。残余的抗CPTIO松弛成分分别相当于对照组和糖尿病组环初始预收缩的26%和4,3%，吲哚美辛、过氧化氢酶、半胱氨酸或四乙铵均未改变该成分，但1H-[1，2，4]恶二唑并[4，3，-a]喹喔啉-1-酮显著抑制该成分。这些数据表明释放了仅使用NO合酶抑制剂无法辨别的额外未知因子。这种抗CPTIO的扩张剂可能不是环加氧酶产物或超极化因子，而是部分通过鸟苷酸环化酶活化起作用的因子。该物质可能是NO，其不能通过其扩散性和螯合或分子重排而与CPTIO反应成氧化还原活性形式（即，NO）或者是完全不同的血管扩张剂。使用更脂溶性的硝酰基氮氧化物衍生物表明，糖尿病（但不是对照）环中的CPTIO抗性松弛的一部分可以通过脂质相中螯合的NO来解释。
Nitronyl nitroxides react with nitric oxide radical (.NO) to form imino nitroxides. We used a nitronyl nitroxide, [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3 oxide] (CPTIO) to evaluate the contribution of .NO to basal tone and acetylcholine-induced endothelium-dependent relaxation in control vs. diabetic rat aortic rings. In rings precontracted with phenylephrine, CPTIO produced an additional increment in tension that was greater in control vs. diabetic rings. Tension after CPTIO was similar to that observed in rings pretreated with the NO synthase inhibitor, L-nitroarginine or in rings without endothelium. This increment was insensitive to indomethacin, cysteine, tetraethylammonium or catalase, but was sensitive to inhibition by the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one. L-Nitroarginine blocked relaxation to ACH by 100 and 90% in control and diabetic rings, respectively. In contrast, CPTIO produced a concentration-dependent inhibition of ACH-induced relaxation that was greater in control rings. The residual CPTIO-resistant component of relaxation was equivalent to 26 and 43% of initial precontraction in control vs. diabetic rings, respectively, and was not altered by indomethacin, catalase, cysteine or tetraethylammonium but was significantly inhibited by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one. These data suggest the release of additional unknown factor(s) that cannot be discerned using NO synthase inhibitors only. This CPTIO-resistant dilator is likely not a cyclooxygenase product or a hyperpolarizing factor but a factor that acts, in part, by activation of guanylate cyclase. This substance is possibly .NO that is not available for reaction with CPTIO either by its diffusibility and sequestration or molecular rearrangement to a redox active form (i.e., not free .NO) or is a completely different vasodilator. The use of a more lipid soluble nitronyl nitroxide derivative suggests a portion of the CPTIO-resistant relaxation in diabetic (but not control) rings could be explained by .NO sequestered in the lipid phase.