Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway.
Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway.
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DOI：
10.1016/j.freeradbiomed.2011.09.020
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发表时间：
2012-01-15
影响因子：
7.4
通讯作者：
Bonini, Marcelo G.
中科院分区：
文献类型：
--
作者：
Mao, Mao;Sudhahar, Varadarajan;Ansenberger-Fricano, Kristine;Fernandes, Denise C.;Tanaka, Leonardo Y.;Fukai, Tohru;Laurindo, Francisco R. M.;Mason, Ronald P.;Vasquez-Vivar, Jeannette;Minshall, Richard D.;Stadler, Krisztian;Bonini, Marcelo G.
硝酸甘油(GTN)临床用于治疗心绞痛和急性心脏病发作已有100多年的历史。GTN的作用早已被认识到，积极的研究有助于解开许多代谢途径，能够将GTN转化为强大的血管活性信使一氧化氮。最近，小剂量GTN引起强烈药理反应的机制被重新讨论，eNOS激活被认为是介导低剂量(1-50 nM)GTN诱导血管扩张的重要途径。在这里，我们证明，在这样的浓度下，硝酸甘油的药理作用在很大程度上依赖于磷脂酰肌醇3-激酶、Akt/PKB以及10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)信号转导轴。此外，我们证明了硝酸甘油依赖的3，4，5-InsP3的积聚可能是由于抑制了PTEN，对eNOS的激活是重要的，这为GTN在药理上相关剂量的药理作用提供了机制基础。
Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1–50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses.
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影响因子：
3
作者：
Otto, Anne;Fontaine, Jeanine;Berkenboom, Guy
通讯作者：
Berkenboom, Guy
影响因子：
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Münzel, T
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作者：
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