Clapp Brian R, Hingorani Aroon D, Kharbanda Rajesh K, Mohamed-Ali Vidya, Stephens Jeffrey W, Vallance Patrick, MacAllister Raymond J
BHF Laboratories, Centre for Clinical Pharmacology, Department of Medicine, University College London, Rayne Institute, 5 University Street, London WC1E 6JJ, United Kingdom.
Cardiovasc Res. 2004 Oct 1;64(1):172-8. doi: 10.1016/j.cardiores.2004.06.020.
Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans.
Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response. Basal and stimulated endothelial nitric oxide (NO) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine (l-NMMA) and bradykinin, respectively. The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress, respectively. Systemic effects were determined by measuring cytokine response, total anti-oxidant status (TAOS) and urinary protein excretion.
Vaccination induced a cytokine response, a fall in total anti-oxidant status and increased urinary albumin excretion (UAE). There was a reduction in the response to bradykinin (BK, P<0.005) and l-NMMA (P<0.0001) with no effect on the response to glyceryl trinitrate (GTN) and norepinephrine (NE). Following vaccination blood flow response to BK (but not GTN) was partially returned to pre-vaccine levels by infusion of ascorbic acid (P=0.01). Supplementation with l-arginine had no effect.
Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction.
我们的目的是研究人类炎症诱导的内皮功能障碍机制。
对21名健康人类志愿者，在接种伤寒疫苗以引发炎症反应之前和之后8小时，使用前臂静脉体积描记法测量内皮功能。分别通过测量对动脉内N（G）-单甲基-L-精氨酸（L-NMMA）和缓激肽的反应，评估基础和刺激状态下的内皮一氧化氮（NO）生物利用度。分别评估补充L-精氨酸或抗坏血酸的效果，以探究底物缺乏和氧化应激的影响。通过测量细胞因子反应、总抗氧化状态（TAOS）和尿蛋白排泄来确定全身效应。
接种疫苗引发了细胞因子反应、总抗氧化状态下降和尿白蛋白排泄增加（UAE）。对缓激肽（BK，P<0.005）和L-NMMA（P<0.0001）的反应降低，而对硝酸甘油（GTN）和去甲肾上腺素（NE）的反应无影响。接种疫苗后，通过输注抗坏血酸，对BK（而非GTN）的血流反应部分恢复到接种前水平（P=0.01）。补充L-精氨酸无效果。
炎症导致广泛的内皮功能障碍，降低血管NO生物利用度并增加氧化应激。这些作用可被局部抗氧化剂部分逆转。这些发现表明活性氧在炎症诱导的内皮功能障碍中起作用。
