Evaluation of nebivolols effects in hypertension and vascular dysfunction induced by experimental pre-eclampsia in rats

• Grant number: 23/04995-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Barbara Rubio de Jesus
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In pre-eclampsia (PE), the hypoxia and ischemia generated by the inefficient development of spiral arteries due to failure of trophoblast invasion causes placental dysfunction and, consequently, generalized endothelial dysfunction. As a result, the dysfunctional placenta releases anti-angiogenic factors, pro-inflammatory antigens, and Reactive Oxygen Species (ROS). Moreover, oxidative stress is also evidenced the reduction of antioxidant enzymes and the uncoupling of the NO-producing enzyme, called eNOS. It was due to these factors that the present study assumes that nebivolol, an antihypertensive drug with antioxidant effects, can be repositioned to treat preeclampsia, proposing a safe and affordable therapy, for this condition that still has no effective pharmacological treatment. For this, the Reduced Uterine Perfusion Pressure (RUPP) model will be used to induce preeclampsia in 32 Wistar female rats, which are divided into the following groups: 1. Normotensive pregnant rats treated with saline solution; 2. Hypertensive pregnant rats treated with saline solution; 3; Normotensive pregnant rats treated with nebivolol 10 mg/kg/day; 4. Hypertensive pregnant rats treated with nebivolol 10 mg/kg/day. The RUPP surgical procedure and euthanasia will be performed on the 14th and 21st gestational days, respectively. Samples of maternal reproductive organs and of maternal arteries will be collected to analyze the effect of the drug on gestational hypertension and oxidative stress.