The role of nitric oxide synthase inhibition by asymmetric dimethylarginine in the pathophysiology of preeclampsia.
Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide. Despite recent advances in screening, sensitive and specific biomarkers that help to identify pregnant women at risk of developing preeclampsia are lacking. One of the major mediators from healthy endothelium is nitric oxide; its production is regulated by asymmetric dimethylarginine (ADMA). ADMA has been shown to be elevated in cardiovascular and metabolic diseases; elevated ADMA levels are a prognostic marker for major cardiovascular events and mortality in patients with established cardiovascular disease and in the general population. Several studies have reported elevated ADMA levels in preeclampsia; some studies also suggested that ADMA is elevated in early stages of pregnancy in women who later develop preeclampsia. Moreover, ADMA has been associated with uterine artery flow disturbances. Its plasma concentration is regulated by dimethylarginine dimethylaminohydrolase (DDAH). Single nucleotide polymorphisms in the gene encoding for DDAH have been associated with the incidence of preeclampsia. Recently, diagnostic assays for ADMA, e.g. by ELISA, have become available, which render ADMA a possible biomarker to identify pregnant women at risk of developing preeclampsia.
Böger
Rainer H
RH
Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf Martinistrasse 52, DE-20246 Hamburg, Germany. boeger @ uke.uni-hamburg.de
Diemert
Anke
A
Schwedhelm
Edzard
E
Lüneburg
Nicole
N
Maas
Renke
R
Hecher
Kurt
K
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D011247:Pregnancy
D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase