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Am J Physiol Regul Integr Comp Physiol 296: R195-R200, 2009. First published August 6, 2008; doi:10.1152/ajpregu.90506.2008
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10th Annual Meeting for New Research in Cardiovascular and Kidney Diseases

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Dan Wang,1,2 Svend Strandgaard,2 Jens Iversen,2 and Christopher S. Wilcox1

1Georgetown University Hypertension, Kidney and Vascular Disorders Center, Division of Nephrology and Hypertension, Georgetown University, Washington, DC; and 2Department of Nephrology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

Submitted 17 June 2008 ; accepted in final form 31 July 2008

We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n = 9) compared with normal controls (n = 10). We now test the hypothesis that the patients in this study have increased circulating levels of the cNOS inhibitor, asymmetric dimethylarginine (ADMA), or the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (HODE), which is a marker of reactive oxygen species. Patients had significantly (P < 0.001) elevated (means ± SD) plasma levels of ADMA (PADMA, 766 ± 217 vs. 393 ± 57 nmol/l) and symmetric dimethylarginine (PSDMA: 644 ± 140 vs. 399 ± 70 nmol/l) but similar levels of L-arginine accompanied by significantly (P < 0.015) increased rates of renal ADMA excretion (21 ± 9 vs. 14 ± 5 nmol/µmol creatinine) and decreased rates of renal ADMA clearance (18 ± 3 vs. 28 ± 5 ml/min). They had significantly increased plasma levels of HODE (PHODE: 309 ± 30 vs. 226 ± 24 nmol/l) and renal HODE excretion (433 ± 93 vs. 299 ± 67 nmol/µmol creatinine). For the combined group of normal and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly (P < 0.001) and inversely correlated with microvascular EDRF/NO and positively correlated with mean blood pressure. In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure.

blood pressure; 13-hydroxyoctadecadienoic acid; endothelium-derived relaxation factor/nitric oxide; albuminuria



Address for reprint requests and other correspondence: C. S. Wilcox, Div. of Nephrology and Hypertension, Georgetown Univ. Medical Center, 3800 Reservoir Rd., NW, PHC F6003, Washington, DC 20007 USA (e-mail: wilcoxch{at}georgetown.edu)







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