Submitted on June 17, 2008
Revised on July 18, 2008
Accepted on July 31, 2008
Asymmetric Dimethylarginine, Oxidative Stress and Vascular Nitric Oxide Synthase in Essential Hypertension
Dan Wang1, Svend Strandgaard2, Jens S Iversen, and Christopher S. Wilcox3*
1 Georgetown University
2 University of Copenhagen
3 Georgetown University Medical Center
* To whom correspondence should be addressed. E-mail: wilcoxch{at}georgetown.edu.
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 to 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 of 13-hydroxyoctadecadienoic acid (HODE) which is a marker of reactive oxygen species (ROS). Patients had significantly (p<0.001) elevated (mean ± SD) plasma levels of ADMA (PADMA, 766 ± 217 vs. 393 ± 57 nmol• L-1) and symmetric dimethylarginine (PSDMA: 644 ± 140 vs. 399 ± 70 nmol• L-1) 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-1) and decreased rates of renal ADMA clearance (18 ± 3 vs 28 ± 5 ml• min-1). They had significantly increased plasma levels of HODE (PHODE: 309 ± 30 vs 226 ± 24 nmol• L-1) and renal HODE excretion (433 ± 93 vs 299 ± 67 nmol• µmol creatinine-1). 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.
