The role of the L-arginine-nitric oxide pathway in preeclampsia.
Preeclampsia (PE) is a major cause of maternal and perinatal mortality, especially in developing countries. Its etiology involves multiple factors, but no specific cause has been identified. Evidence suggests that clinical manifestations are caused by endothelial dysfunction. Nitric oxide (NO), which is synthesized from L-arginine in endothelial cells by the endothelial nitric oxide synthase (eNOS), provides a tonic dilator tone and regulates the adhesion of white blood cells and platelet aggregation. Alterations in the L-arginine-NO pathway have been associated with the development of PE. Various studies, reporting decreased, elevated or unchanged levels of nitrite (NO(2)) and nitrate (NO(3)), two end products of NO metabolism, have been published. Our group contributed to those contradictory reports describing cases of PE with both elevated and decreased levels of NO(2) and NO(3). Apparently, diminished levels of NO could be related to deficiencies in the ingestion of dietary calcium associated to low levels of plasma ionic calcium, which is crucial to the eNOS' activity. Also, low levels of NO could be associated with the presence of eNOS polymorphisms or the presence of increased levels of ADMA, the endogenous inhibitor of NO. High levels of NO associated to low levels of cGMP suggest a decreased bioactivity of NO, which is probably related to an increased degradation of NO caused by a high production of superoxide in states of infection and inflammation. The present article analyses and reviews the reported paradoxical roles of the L-arginine-NO pathway in PE and gives a possible explanation for these results.
López-Jaramillo
Patricio
P
VILANO Group, Research Institute, Fundación Cardiovascular de Colombia, Floridablanca, Santander, Colombia. joselopez@fcv.org
Arenas
William D
WD
García
Ronald G
RG
Rincon
Melvin Y
MY
López
Marcos
M
D001120:Arginine / Q000378:metabolism*; D001810:Blood Volume; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy
D009569:Nitric Oxide; D001120:Arginine