Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats

Preeclampsia is a maternal hypertension disorder associated with vascular dysfunction and fetal and placental growth restrictions. Placental ischemia is suggested as the primary trigger of preeclampsia-associated impairments of both endothelium-derived nitric oxide (NO) and the vascular activity of...

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Published in:International journal of molecular sciences 2023-08, Vol.24 (16), p.12818
Main Authors: Martins, Laisla Zanetoni, da Silva, Maria Luiza Santos, Rodrigues, Serginara David, Gomes, Sáskia Estela Biasotti, Molezini, Laura, Rizzi, Elen, Montenegro, Marcelo Freitas, Dias-Junior, Carlos Alan
Format: Article
Language:English
Subjects:
Bioavailability
Blood pressure
Coronary vessels
Endothelium
Extracellular matrix
Hypertension
Hypoxia
Ischemia
Metabolites
metalloproteinase-2
Nitric oxide
Pathogenesis
placental ischemia
Preeclampsia
Pregnancy
Sodium
sodium nitrite
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Summary:Preeclampsia is a maternal hypertension disorder associated with vascular dysfunction and fetal and placental growth restrictions. Placental ischemia is suggested as the primary trigger of preeclampsia-associated impairments of both endothelium-derived nitric oxide (NO) and the vascular activity of extracellular matrix metalloproteinase-2 (MMP-2). Reduced uteroplacental perfusion pressure (RUPP) is a placental ischemia model of preeclampsia. Reduction of sodium nitrite to NO may occur during ischemic conditions. However, sodium nitrite effects in the RUPP model of preeclampsia have not yet been investigated. Pregnant rats were divided into four groups: normotensive pregnant rats (Norm-Preg), pregnant rats treated with sodium nitrite (Preg + Nitrite), preeclamptic rats (RUPP), and preeclamptic rats treated with sodium nitrite (RUPP + Nitrite). Maternal blood pressure and fetal and placental parameters were recorded. Vascular function, circulating NO metabolites, and the gelatinolytic activity of vascular MMP-2 were also examined. Sodium nitrite attenuates increased blood pressure, prevents fetal and placental weight loss, counteracts vascular hyper-reactivity, and partially restores NO metabolites and MMP-2 activity. In conclusion, sodium nitrite reduction to NO may occur during RUPP-induced placental ischemia, thereby attenuating increased blood pressure, fetal and placental growth restriction, and vascular hyper-reactivity associated with preeclampsia and possibly restoring NO and MMP-2 activity, which underlie the blood pressure-lowering effects.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241612818