Vascular Endothelial Cell Activation Associated with Increased Plasma Asymmetric Dimethyl Arginine in Children and Young Adults with Hypertension: A Basis for Atheroma?

• Published in: Blood pressure 2000, Vol.9 (1), p.16-21
• Main Author: GOONASEKERA, CHULANANDA D. A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Arginine - analogs & derivatives; Arginine - blood; Arterial hypertension. Arterial hypotension; Arteriosclerosis - etiology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Child; Child, Preschool; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Female; Glomerular Filtration Rate; Humans; Hypertension - blood; Hypertension - complications; Hypertension - physiopathology; Infant; Male; Medical sciences; Vascular Cell Adhesion Molecule-1 - blood
• ISSN: 0803-7051; 1651-1999
• DOI: 10.1080/080370500439371

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.