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

• Grant number: 23/06195-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Cristal de Jesus Toghi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 21/12010-7 - Endothelial dysfunction in hypertensive disorders of pregnancy, AP.TEM
• Associated scholarship(s): 24/15207-4 - Evaluation of endothelial dysfunction in experimental model of preeclampsia-like symptoms induced by reduction of uterine perfusion pressure (RUPP) in pregnant rats, BE.EP.DD

Abstract

Nitric oxide (NO) is a critical endogenous mediator involved in various physiological aspects of healthy pregnancy, including implantation, placental perfusion, maternal systemic vasodilation, and renal adaptation during pregnancy. NO deficiency during pregnancy has been associated with various hypertensive disorders, such as preeclampsia (PE). S-nitrosylation represents the major route for NO to regulate protein functions, and S-nitrosothiols are potent vasodilators, capable of inhibiting the activation of the angiotensin type 1 receptor (AT1), which is related to the induction of cardiovascular dysfunction observed in PE. Beet juice-derived nitrate (NO3) has been proposed as a new therapeutic approach to treat PE, as it has been shown to reduce maternal hypertension and other adverse fetal outcomes in an animal model similar to eclampsia. Therefore, this study aims to evaluate the impact of nitrate treatment on total protein nitrosylation and AT1 receptor in the cardiovascular system and its possible implications in the pathogenesis of PE in an experimental model. To achieve this objective, pregnant rats will be divided into four groups: normotensive pregnant rats (Norm-Preg), normotensive pregnant rats treated with nitrate (Preg+Nitrate), rats subjected to the reduced uterine perfusion pressure (RUPP) model, and rats subjected to the RUPP model treated with nitrate (RUPP+Nitrate). To induce PE-like symptoms, pregnant rats will be subjected to the RUPP model. The rats' blood pressure, fetal and placental weights will be recorded, and cardiac structural and functional parameters will be evaluated using echocardiography, and endothelial function through vascular reactivity technique. In addition, the nitrosylation of AT1 receptor, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PLGF) will be measured. The hypothesis is that oral nitrate treatment will increase circulating levels of S-nitrosylated species and promote vascular nitrosylation of AT1 receptor, preventing adverse negative outcomes in PE. (AU)