Letter to the Editor

Abstract

Noris et al describe that preeclamptic women have decreased placental villi L-arginine concentration and overexpression of arginase II. 1 In February, Alexander et al reported that supplementing L-arginine in pregnant rats with reduced uterine perfusion decreased blood pressure, concomitantly increasing serum L-arginine levels and urinary nitrite/nitrate. 2 Both reports highlight the role of the L-arginine-nitric oxide (NO) pathway in determining normal and preeclamptic pregnancies and sustain the potential benefit of L-arginine supplementation in women at risk of preeclampsia. Although L-arginine has been given acutely to preeclamptic women, there is no concordance about its benefits. 3,4 We wish to underscore the benefits of this intervention with our experience with chronic long-term oral L-arginine supplementation in women at risk of placentation-related disorders.Seventeen women with bilateral notching and high uterine artery resistance in transvaginal ultrasounds performed 2 weeks apart (Ϫ2 and 0 weeks) were included. Endothelial function was also assessed by high-resolution ultrasound of the brachial artery. Of the 15 multiparas, 3 had presented preeclampsia associated with stillbirth in 2, 5 had unexplained recurrent abortions, 2 had isolated spontaneous abortions, and 1 had a premature delivery of ischemic origin. None presented thrombophilias. L-Arginine supplementation (0.1 g/kg per day PO; Smartbasics, San Francisco, Calif) was started at 10.1Ϯ0.9 (SEM) weeks of gestation (week 0), and continued until delivery. After 2 weeks on L-arginine, the women's mean arterial pressure and uterine artery resistance index decreased (75Ϯ2 versus 82Ϯ3 and 80Ϯ2 mm Hg; 0.76Ϯ0.01 versus 0.89Ϯ0.02 and 0.87Ϯ0.01 and at Ϫ2 and 0 weeks respectively; PϽ0.05 for 2 versus 0 and Ϫ2 weeks for both values), and endothelial-mediated vasodilatation improved (10.9%Ϯ1.0% versus 7.7%Ϯ1.9% and 5.5%Ϯ1.2%; PϽ0.05 for 2 versus Ϫ2 weeks). All women delivered at term (38.0Ϯ1.1 week), and excepting 1, had infants of normal weight (3227Ϯ371 g); one woman developed a moderate preeclampsia ( 2 ϭ12.5, PϽ0.001 for the combination of live births, perinatal outcome, and preeclampsia versus the preceding pregnancy). Maternal tolerance to supplementation was adequate; the offsprings presented no side effects at birth or during 2 to 48 months follow-up.Our data show that the acute enhancement of the L-arginine-NO pathway ameliorates the local and systemic adaptations of pregnancy. While the improvement of the perinatal outcome could represent a spontaneous remission, a beneficial effect of L-arginine is suggested, because 9 out of 17 women previously presented 2 or more placentation-related complications of pregnancy, and patients with this clinical history have recurrence rates of preeclampsia or pregnancy loss of 40% to 60%, respectively. Moreover, all women included in this intervention presented in early pregnancy bilateral notching of the uterine arteries, index associated to odds ratio of 42.02, 8.61, and 2.38 for preeclampsia, fetal growth r...

Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis

“…Rytlewski K et al [ 15 ] demonstrated a significant increase in estimated fetal body weight after the first two weeks of treatment in their L-arginine group compared to the placebo group. However, the results from other trials were different [ 27 , 28 ]. Therefore, more studies are necessary to clarify these results.…”

Roles of Nitric Oxide and Asymmetric Dimethylarginine in Pregnancy and Fetal Programming

“…Some favorable effects of supplemental l -arginine on blood pressure and pregnancy outcomes were reported in patients with preeclampsia [93]. However, the data from human trials remain inconclusive.…”

Is the serum L-arginine level during early pregnancy a predictor of pregnancy-induced hypertension?

“…( 10 , 11 ) It was already recommended that l -arginine be examined in clinical trials in high risk pregnancies ten years ago. ( 12 ) Recently, a clinical study investigated the effect of supplementations during pregnancy with l -arginine and antioxidant vitamins, and demonstrated that the intervention reduced the incidence of preeclampsia in a Mexican population at high risk of the condition. ( 13 ) With the increased need of NO to support the adaptive vasodilatation, the maternal l -arginine level has been shown to be deficient during pregnancy due to consumption by the fetus.…”