Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension.
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 (P(ADMA), 766 +/- 217 vs. 393 +/- 57 nmol/l) and symmetric dimethylarginine (P(SDMA): 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/mumol creatinine) and decreased rates of renal ADMA clearance (18 +/- 3 vs. 28 +/- 5 ml/min). They had significantly increased plasma levels of HODE (P(HODE): 309 +/- 30 vs. 226 +/- 24 nmol/l) and renal HODE excretion (433 +/- 93 vs. 299 +/- 67 nmol/micromol 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.
Wang
Dan
D
Georgetown University Hypertension, Kidney and Vascular Disorders Center, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007 USA.
Strandgaard
Svend
S
Iversen
Jens
J
Wilcox
Christopher S
CS
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D001794:Blood Pressure; D002081:Buttocks; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008041:Linoleic Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D055806:Microvessels / Q000201:enzymology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress; D040521:Subcutaneous Tissue / Q000098:blood supply*; D015854:Up-Regulation; D014664:Vasodilation; D055815:Young Adult
D045462:Endothelium-Dependent Relaxing Factors; D008041:Linoleic Acids; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C024348:13-hydroxy-9,11-octadecadienoic acid; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase