Comparative evaluation of the sodium nitrate effects on vascular reactivity to angiotensin II and phenylephrine in a preeclampsia model induced by placental ischemia in rats

• Grant number: 25/13569-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Aurélio Henrique Doreto
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Nitric oxide (NO) is an endogenous mediator essential for maintaining vascular function during pregnancy, playing a key role in systemic vasodilation and regulation of peripheral vascular resistance. In preeclampsia, a specific hypertensive disorder of pregnancy, NO synthesis and bioavailability are impaired, contributing to endothelial dysfunction, increased vasoconstriction, and elevated blood pressure, making it one of the main causes of maternal morbidity and mortality worldwide. In this context, therapeutic strategies that increase NO bioavailability have been investigated as promising alternatives to mitigate the vascular alterations characteristic of the disease. Thus, this study aims to evaluate the effects of oral sodium nitrate treatment on vascular function and reactivity to vasoconstrictor agonists in an experimental model of preeclampsia. Pregnant rats will be divided into four experimental groups: normotensive pregnant (Norm-Preg), normotensive pregnant treated with sodium nitrate (Norm-Preg+Nitrate), pregnant rats subjected to the reduced uteroplacental perfusion pressure model (RUPP), and RUPP rats treated with sodium nitrate (RUPP+Nitrate). The RUPP model will be used to induce clinical signs of placental ischemia, reproducing key pathophysiological features of preeclampsia. Systolic blood pressure, fetal and placental weights, vascular reactivity to angiotensin II and phenylephrine, NO bioavailability, and oxidative stress markers will be assessed to test the hypothesis that sodium nitrate may enhance NO production, reduce vascular hyperreactivity, and help preserve endothelial integrity under experimental conditions that mimic preeclampsia.