Sodium nitrite reduces circulating asymmetric dimethylarginine in a reduced uterine perfusion pressure rat model of preeclampsia.

Introduction: Preeclampsia (PE) is characterized by hypertension, endothelial dysfunction, and reduced nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial NO synthase, is elevated in PE and contributes to vascular dysfunction. NO may regulate ADMA production. NO formation from nitrite occurs under hypoxic-ischemic conditions. Thus, this study investigated whether sodium nitrite attenuates circulating ADMA levels and vascular endothelial dysfunction in placental ischemia induced by reduced uteroplacental perfusion pressure (RUPP) in pregnant rats. Methods: Pregnant Wistar rats were assigned to Sham, RUPP, Sham-Nitrite, and RUPP-Nitrite groups. Sodium nitrite (15 mg/kg/day) was administered orally from gestational day 14-21. Results: RUPP rats exhibited increased systolic, diastolic, and mean arterial pressure, reduced fetal and placental weights, impaired acetylcholine-induced relaxation, enhanced phenylephrine-induced vasoconstriction, and increased plasma ADMA levels compared to Sham group. Sodium nitrite treatment attenuated hypertension, improved fetal and placental parameters, partially restored endothelial function and reduced vascular hyper-reactivity. Plasma NO metabolites in the RUPP-Nitrite group were not significantly different from Sham. Importantly, sodium nitrite markedly attenuated the RUPP-induced increases in circulating ADMA, suggesting modulation of the ADMA-NO pathway in experimental PE. Discussion: These findings indicate that nitrite treatment may attenuate endothelial dysfunction and vascular impairment associated with placental ischemia, potentially involving modulation of circulating ADMA.