Vascular endothelial cell activation associated with increased plasma asymmetric dimethyl arginine in children and young adults with hypertension: a basis for atheroma?
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 level of the endogenous nitric oxide inhibitor asymmetric dimethyl arginine (ADMA) in a group of 31 (17 male, mean age 9.4 years) hypertensive and 9 (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.
Goonasekera
C D
CD
Nephrourology Unit, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK.
Shah
V
V
Rees
D D
DD
Dillon
M J
MJ
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001161:Arteriosclerosis / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007223:Infant; D008297:Male; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D019010:Vascular Cell Adhesion Molecule-1; C018524:N,N-dimethylarginine; D001120:Arginine