Mavrikakis Myron E, Lekakis John P, Papamichael Christos M, Stamatelopoulos Kimon S, Kostopoulos Ch C, Stamatelopoulos Stamatios F
Department of Clinical Therapeutic, Alexandra University Hospital, Athens, Greece.
Int J Vitam Nutr Res. 2003 Feb;73(1):3-7. doi: 10.1024/0300-9831.73.1.3.
Previous studies have shown that patients with Raynaud's phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud's phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud's phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud's phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 +/- 2.2% to 2.2 +/- 2.5%, ns) or placebo administration (1.2 +/- 1.9% to 1.7 +/- 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 +/- 7.4% vs 17 +/- 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud's phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.
以往研究表明，继发于系统性硬化症的雷诺现象患者存在内皮功能异常；导致内皮功能障碍的机制尚不清楚，但血管氧化应激增加可能是一个潜在原因。本研究对一种强效水溶性抗氧化剂能否逆转这些患者的内皮功能障碍这一假设进行了验证。我们通过对肱动脉进行超声成像，检测了11名继发于系统性硬化症的雷诺现象女性患者和10名健康对照女性，以评估血流介导的（内皮依赖性）和硝酸盐诱导的（非内皮依赖性）血管舒张功能。雷诺现象患者的血流介导的血管舒张和硝酸盐诱导的血管舒张均显著降低，表明内皮和平滑肌细胞功能异常。雷诺现象患者进入一项双盲、随机、交叉、安慰剂对照试验，口服2 g抗坏血酸或安慰剂；在给予抗坏血酸或安慰剂两小时后重复进行血管研究。给予抗坏血酸后（从1.6±2.2%至2.2±2.5%，无显著差异）或安慰剂后（从1.2±1.9%至1.7±1.4%，无显著差异），血流介导的血管舒张均未改善；同样，给予抗坏血酸或安慰剂后硝酸盐诱导的血管舒张也相似（分别为16±7.4%和17±8%，无显著差异），提示抗坏血酸对内皮和血管平滑肌功能无影响。总之，抗坏血酸不能逆转继发于系统性硬化症的雷诺现象患者肱动脉循环中的内皮血管舒缩功能障碍。可能需要使用不同的抗氧化剂或不同剂量的抗坏血酸才能对内皮血管舒张功能产生有益影响。
