Evaluation of endothelial dysfunction in experimental model of preeclampsia-like symptoms induced by reduction of uterine perfusion pressure (RUPP) in pregnant rats

• Grant number: 24/15207-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 06, 2025
• End date: January 05, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Cristal de Jesus Toghi
• Supervisor: Ana Carolina Taveiros Palei
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: University of Mississippi Medical Center (UMMC), United States
• Associated to the scholarship: 23/06195-0 - Evaluation of endothelial dysfunction in experimental model of preeclampsia-like symptoms induced by reduction of uterine perfusion pressure (RUPP) in pregnant rats, BP.DD

Abstract

Hypertensive pregnancy disorders are a worthy cause of maternal and fetal mortality. Among them, preeclampsia/eclampsia is more severe and is characterized by elevations in maternal blood pressure along with end-organ failure which may compromise fetal development. The pathogenesis is still unknown, but there are theories that an impairment occurs in the plasticity of the vessels of the maternal-fetal interface, placental ischemia accompanied by maternal endothelial dysfunction. In this context, nitric oxide (NO) deficiency during pregnancy has been associated with various hypertensive disorders, including preeclampsia (PE). Nitrate has been proposed as a new therapeutic approach to treat cardiovascular diseases, because it has been shown to reduce blood pressure and its effects are related to the S-nitrosylation. S-nitrosylation represents the major route for NO, derived from nitrate (NO3), to regulate protein functions, and S-nitrosothiols are potent vasodilators, capable of inhibiting the activation of the angiotensin II type 1 receptor (AT1), which is related to the induction of cardiovascular dysfunctions. However, no previous study has assessed the effects of nitrate in PE. Therefore, this study aims to evaluate the impact of nitrate treatment on cardiac function and on total protein nitrosylation and AT1 receptor in the heart and aorta segments from pregnant rats submitted to the PE model induced by reduced uterine perfusion pressure (RUPP). To achieve this objective, pregnant rats will be divided into four groups: normotensive pregnant rats (Norm-Preg), normotensive pregnant rats treated with nitrate (Norm-Preg+Nitrate), rats subjected to the RUPP model, and rats subjected to the RUPP model and treated with nitrate (RUPP+Nitrate). The maternal blood pressure, fetal and placental weights will be recorded, and cardiac structural and functional parameters will be evaluated using echocardiography method. The hypothesis is that nitrate treatment (by gavage) will increase circulating levels of S-nitrosylated species and promote cardiac and vascular nitrosylation of AT1 receptor, thus preventing adverse and negative cardiovascular outcomes in PE.Keywords: cardiac dysfunction, gestational hypertension, preeclampsia, nitrate, S-nitrosylation, angiotensin II type 1 receptor.