Effect of L-Arginine supplementation on endothelial function and L-Arginine/ADMA ratio in women with previous prececlampsia or recurrent pregnancy loss

Abstract

Objetive: To evaluate the effect of the L-Arginine supplementation on the brachial artery flow mediated dilatation (FMD) as an index of endothelial function, uterine artery vascular resistance (UAVR) and on the L-Argine/ADMA ratio in women with previous preeclampsia (PE) or recurrent pregnancy loss (RPL) far from pregnancy. Design: In a double blind, crossover, placebo controlled trial, 16 women with severe endothelial dysfunction (FMD <4.5%; SED) without thrombophilia were randomized to receive placebo or L-Arginine (0.1g/kg/day) during 3 consecutive menstrual cycles, with one middle cycle of wash-out period. FMD (Vascular ultrasound), UAVR (Transvaginal Color Doppler ultrasound) and the plasma L-Arginine/ADMA ratio (HPLC) were assessed before and after each treatments. Results (expressed as Mean±SE): The L-Arginine supplementation significantly rise FMD compared with basal and placebo intervention (11.8±2.7% v/s 0.1±1.1% v/s 2.3±1.4% respectively; p<0.001). The L-Arginine/ADMA ratio increased significantly in 53% and 42% compared with basal and placebo. No changes in UAVR were observed. Conclusion: In patients with SED and previous PE or RPL, L-Arginine supplementation improve the endothelial function through removal of the endogenous competitive eNOS inhibitor, ADMA. This suggest that an abnormal L-Arginine metabolism is present in a subset of this patients. In those patients, the secondary prevention with L-Arginine during the pregnancy could prevents the high recurrence of PE or RPL observed. The molecular basis of the abnormal L-Arginine metabolism remain to be investigated. Supported by a Grant from Gynopharm Laboratory (Recalcine Group)