Vascular endothelial cell activation associated with increased plasma asymmetric dimethyl arginine in children and young adults with hypertension: A basis for atheroma?

被引:51
作者
Goonasekera, CDA
Shah, V
Rees, DD
Dillon, MJ
机构
[1] Inst Child Hlth, Nephrourol Unit, London WC1N 1EH, England
[2] Great Ormond St Hosp Sick Children, London WC1N 3JH, England
[3] UCL, Dept Clin Pharmacol, London, England
关键词
asymmetric dimethyl arginine; children; hypertension; vascular endothelium; VCAM-1;
D O I
10.1080/080370500439371
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The mechanism behind the development of vascular complications of hypertension in the young human remains unclear. To explore the role of vascular endothelium-generated nitric oxide (a known mediator of leucocyte-platelet-endothelial interactions) in this context, we investigated markers of endothelial activation (soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin. E-selectin), and von Willebrand factor and the plasma lever of the endogenous nitric oxide inhibitor asymmetric dimethyl arginine (ADMA) in a group of 31 (17 male. mean age 9.4 years) hypertensive and (4 male, mean age 9.1 years) healthy, normotensive children and young adults. We found raised levels of ADMA (mean (SEM) 235 (32) n mol/l) and VCAM-1 (median (range) 1237 (675-2700) ng/ml) in the plasma of hypertensive subjects compared with those of normotensives (ADMA 103 (7)n mol/l and VCAM-1, 1005 (425-1650) ng/ml, respectively), Furthermore, in hypertensive subjects, higher VCAM-1 concentrations (r = 0.66, p < 0.001) and vWF concentrations (r = 0.37, p = 0.04) were significantly associated with a higher plasma ADMA level. Therefore. an isolated increase in plasma VCAM-1 in hypertensives in association with raised ADMA may signify a selective "non-inflammatory" endothelial activation triggered by endothelial nitric oxide synthase inhibition. Since VCAM-1 is implicated in the origins of atherosclerosis, ADMA may be an important contributory factor in increasing the risk of atheroma formation in hypertensive children and young adults.
引用
收藏
页码:16 / 21
页数:6
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