Endogenous inhibitors of nitric oxide and preeclampsia: A review

Abstract

Nitric oxide (NO) is a potent vasodilator. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia.

New therapeutic approaches to treating hypertension in pregnancy

“…Moreover, elevated ADMA levels have been found in preeclampsia before the appearance of clinical signs, which might diminish NO bioavailability to a greater extent [12] (Fig. 1).…”

“…In the endothelium, this gas is primarily, if not exclusively, synthesized from the semi-essential cationic amino acid Larginine by endothelial NO synthase (eNOS), and this synthesis can be inhibited naturally by asymmetrical dimethylarginine (ADMA) [12]. Alterations in the synthesis and/or biological actions of NO have been related to abnormal blood flow in disorders of pregnancy that present as different entities but appear to share a common origin: the presence of placental endothelial dysfunction.…”

“…Increased NO synthesis is responsible for a significant part of the maternal vascular adaptation to pregnancy, which is favored by the presence of low levels of ADMA in normal pregnancies [12]. In addition to ADMA, NO bioavailability is regulated by other factors, including relaxin.…”

Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood

“…The released amounts are sufficient to inhibit endogenous NO production. Recent clinical and experimental investigations have indicated that ADMA is both a strong marker and a mediator of many aspects of endothelial dysfunction syndrome, including not only cardiovascular and renal diseases but also preeclampsia [3][4][5][6]. At present, little information is available about the potential physiological roles of ADMA in a perinatal setting.…”

Comparison of maternal serum and umbilical cord concentrations of nitric oxide and asymmetric-dimethyl-arginine in pre-eclamptic and uncomplicated pregnancies

“…Elevated ADMA levels in preeclampsia are detected before clinical symptoms develop; hence these findings suggest that ADMA may play a role in the pathogenesis of preeclampsia (Slaghekke et al, 2006).…”