Nitric Oxide Production and Endothelium-Dependent Vasorelaxation Ameliorated by N1-Methylnicotinamide in Human Blood Vessels
Nitric Oxide Production and Endothelium-Dependent Vasorelaxation Ameliorated by N1-Methylnicotinamide in Human Blood Vessels
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DOI：
10.1161/hypertensionaha.111.183210
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发表时间：
2012-04-01
期刊：
影响因子：
8.3
通讯作者：
Kalinowski, Leszek
中科院分区：
文献类型：
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作者：
Domagala, Teresa B.;Szeffler, Agata;Kalinowski, Leszek
N-1-甲基烟酰胺（MNA（+））直到最近才被认为是吡啶核苷酸途径中烟酰胺代谢的生物学无活性产物。然而，最新的观察结果表明，MNA（+）可能通过直接作用于内皮发挥抗血栓形成和抗炎作用。我们在体内和体外研究了该化合物是否可以通过改善一氧化氮（NO）的生物利用度和减少内皮NO合酶（eNOS）功能介导的氧化应激来诱导人体血管舒张。在胆固醇正常和高胆固醇血症的健康受试者中，MNA（+）治疗（口服100 mg/m2）增加了L-精氨酸（L-NMMA）可耐受的肱动脉血流介导的扩张（FMD）反应，这也与MNA（+）血浆浓度呈正相关（正常胆固醇血症者r=0.73，高胆固醇血症者r=0.78; P
N-1-methylnicotinamide (MNA(+)) has until recently been thought to be a biologically inactive product of nicotinamide metabolism in the pyridine nucleotides pathway. However, the latest observations imply that MNA(+) may exert antithrombotic and anti-inflammatory effects through direct action on the endothelium. We examined both in vivo and in vitro whether the compound might induce vasorelaxation in human blood vessels through the improvement of nitric oxide (NO) bioavailability and a reduction of oxidative stress mediated by endothelial NO synthase (eNOS) function. MNA(+) treatment (100 mg/m(2) orally) in healthy normocholesterolemic and hypercholesterolemic subjects increased the L-arginine (L-NMMA)-inhibitable flow-mediated dilation (FMD) of brachial artery responses that also positively correlated with MNA(+) plasma concentrations (r=0.73 for normocholesterolemics and r=0.78 for hypercholesterolemics; P