Evaluation of the effects of the treatment with nitrite of sodium in the gelatinolytic activity of metalloproteinases 2 and 9 in a model of gestational hypertension in rats

Author(s)

Laisla Zanetoni Martins

• Document type: Master's Dissertation
• Press: Botucatu. 2023-09-20.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2023-08-23
• Advisor: Carlos Alan Candido Dias Junior

Abstract

Preeclampsia (PE) is a maternal hypertension disorder associated with vascular dysfunction and fetal and placental growth restrictions. Placental ischemia is suggested as the primary trigger of PE-associated impairments of both endothelium-derived nitric oxide (NO) and vascular activity of extracellular matrix metalloproteinase-2 (MMP-2). Reduced uteroplacental perfusion pressure (RUPP) is a placental ischemia model of PE. Reduction of sodium nitrite to NO may occur during ischemic conditions. However, sodium nitrite effects in the RUPP model of PE have not yet been investigated. Therefore, the present study investigated the reduction of sodium nitrite to NO during ischemic conditions (RUPP) and whether restoration of circulating NO bioavailability protects against gestational hypertension and vascular dysfunction associated with reduced gelatinolytic activity of MMP-2. 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, fetal and placental parameters were recorded. Vascular function, cir-culating NO metabolites, and gelatinolytic activity of vascular MMP-2 were also examined. So-dium nitrite attenuates pregnancy hypertension, prevents fetal and placental weight loss, coun-teracts 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 pregnancy hypertension, fetal and placental growth restriction, and vascular hyper-reactivity associated with PE, and possibly restoring NO levels and MMP-2 activity underlies the antihypertensive effects. (AU)

• FAPESP's process: 21/03794-4 - Evaluation of the effects of treatment with Sodium Nitrite on the gelatinolytic activity of Metalloproteinases 2 and 9 in a model of gestational hypertension in rats
• Grantee: Laisla Zanetoni Martins
• Support Opportunities: Scholarships in Brazil - Master