Dietary supplement with vitamin C prevents nitrate tolerance
Dietary supplement with vitamin C prevents nitrate tolerance
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DOI：
10.1172/jci977
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发表时间：
1998-07-01
影响因子：
15.9
通讯作者：
Fink, B
中科院分区：
文献类型：
--
作者：
Bassenge, E;Fink, N;Fink, B
超氧自由基形成的增强被认为在人类硝酸盐耐受性的发展中发挥着重要作用。我们在 9 名健康受试者中测试了维生素 C (Vit-C) 补充剂对三硝酸甘油 (GTN) 诱导的血液动力学影响的影响，该影响是在 9 名健康受试者 3 天不间断透皮给药 GTN（0.4 毫克/小时）期间进行的。通过动脉压、重搏脉压和心率的变化来监测耐受性的发展。 GTN、Vit-C 或 GTN/Vit-C 的研究在同一受试者的三个不同系列中连续随机进行。 GTN 治疗导致动脉电导率（重搏脉搏的 alb 比率）立即上升，但在开始 GTN 后 2 天内，alb 比率逐渐下降并达到基础水平。此外，血压的直立性降低逐渐消失。然而，Vit-C 和 GTN 的共同给药完全维持了 GTN 引起的直立血压变化，并且在测试期间白蛋白比率的上升增加了 310%。 GTN 治疗组血管耐受性的变化与分离血小板活性的上调同时发生，而维生素 C 的给药也可逆转这种情况。这些发现表明，在人体长期不间断施用 GTN 期间，膳食补充 Vit-C 可消除血管耐受性，并同时上调离体洗涤的血小板活性。
Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We tested the effects of vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h) in nine healthy subjects. Tolerance development was monitored by changes in arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three different series in the same subjects. GTN treatment caused an immediate rise in arterial conductivity (alb ratio of dicrotic pulse), but within 2 d of initiating GTN, the alb ratio progressively decreased and reached basal levels. In addition, there was a progressive loss of the orthostatic decrease in blood pressure. However, coadministration of Vit-C and GTN fully maintained the GTN-induced changes in the orthostatic blood pressure, and the rise of alb ratio was augmented by 310% for the duration of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated platelets, which was also reversed by Vit-C administration. These findings demonstrate that dietary supplementation with Vit-C eliminates vascular tolerance and concomitant upregulation of ex vivo-washed platelet activity during long-term nonintermittent administration of GTN in humans.