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

Abstract

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.