Evaluation of the effects of metformin on hypertension and endothelial dysfunction induced by a rat experimental model of preeclampsia

• Grant number: 25/08141-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Sarah Daniela Moura Sanches
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Abstract Preeclampsia (PE) is a gestational hypertensive syndrome that affects approximately 2 to 8% of pregnant women and is one of the leading causes of maternal-fetal morbidity and mortality. The pathophysiology of PE involves abnormal placentation, endothelial dysfunction, and systemic inflammation, but effective pharmacological treatment is still lacking. The objective of this study is to explore the therapeutic potential of metformin in an experimental model of PE induced in rats, given the need for new therapeutic approaches targeting the pathophysiological mechanisms of PE. Wistar rats will be divided into four groups: normal treated with saline or metformin, and PE treated with saline or metformin. Experimental PE will be induced by the surgical RUPP model, which consists of reducing uterine perfusion pressure. Metformin will be administered by gavage after the RUPP surgery, starting on the 14th day of gestation. Blood pressure, fetal and placental parameters, bioavailability of nitric oxide metabolites, concentration of antiangiogenic factors, and vascular reactivity will be evaluated. Data will be statistically analyzed using two-way ANOVA followed by Bonferroni's post-hoc test, with a significance level of p < 0.05. This study aims to contribute to the development of new therapeutic strategies for PE by exploring the influence of metformin on maternal endothelial function and fetal viability. Keywords: preeclampsia, metformin, RUPP, oxidative stress, endothelial dysfunction, inflammatory parameters.