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

• Grant number: 21/03794-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2022
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Laisla Zanetoni Martins
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The gestational period is marked by several systemic adaptations, including cardiovascular, necessary for a healthy pregnancy, meeting the fetal metabolic demand. Pre-eclampsia (PE) is a complication of pregnancy with pathogenesis that is still unclear, but it is characterized by elevated maternal blood pressure. In a healthy pregnancy there is a normal trophoblastic invasion and formation of blood vessels at the maternal-fetal interface, however in cases of PE this invasion is deficient and the modification of the maternal arteries is incomplete, reducing the passage of placental blood flow causing hypoxia and ischemia, raising blood pressure. These changes can be modulated by endogenous nitric oxide (NO) and by Matrix Metalloproteinases (MMPs), especially the MMP-2 and MMP-9 gelatinases that can contribute to the increase of vasoconstrictors and reduction of vasodilators. Studies suggest that NO modulates MMP activity and an imbalance in MMP activity may be associated with PE and hypertension in pregnancy. An interesting alternative has been NO derived from sodium nitrite. The experimental model of induction of gestational hypertension and PE known as RUPP (Reduction of Uteroplacental Perfusion Pressure) has been shown to be one of the best for demonstrating most of the responses observed in human PE. Our hypothesis is that the reductions in NO bioavailability caused by the RUPP model could increase the activity of MMPs in pregnancy. Thus, this study seeks to investigate whether the reduction of circulating NO in gestational hypertension caused by RUPP is related to changes in the activities of MMP-2 and MMP-9, in addition to investigating whether treatment with sodium nitrite, which is reduced in NO can mitigate these changes induced by RUPP.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARTINS, Laisla Zanetoni. 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. 2023. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.