Evaluation of the participation of beta-3 adrenergic receptor and nitric oxide synthase in endothelial dysfunction induced by placental ischemia in pregnant rats treated with nebivolol.

• Grant number: 25/10700-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Beatriz Dragoneti Jorge
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia is a hypertensive disorder of human pregnancy, characterized by hypertension associated with proteinuria or target organ damage. It is one of the main causes of maternal and fetal mortality worldwide, especially in lower-income countries. In Brazil, the data is underestimated, but it is estimated that preeclampsia affects at least 1.5% of pregnancies in the country. Although its pathogenesis is not fully understood, its pathophysiology is characterized by oxidative stress, endothelial dysfunction and impaired trophoblastic invasion of the spiral arteries. This complex multifactorial scenario culminates in an imbalance of angiogenic factors and reduced bioavailability of nitric oxide (NO). The syndrome still has no cure, and current treatment consists of alleviating the symptoms or terminating the pregnancy and removing the placenta. Nebivolol is a third-generation beta-blocker that acts on beta-1 and alpha-1 receptors to attenuate hypertension, as well as having the ability to increase NO production possibly through phosphorylation of the enzyme nitric oxide synthase and acting on the beta-3 receptor. Therefore, this project will use the Reduced Utero-placental Perfusion Pressure (RUPP) model to induce preeclampsia in rats. Pregnant rats will be divided into experimental groups: Norm-Preg (sham-operated pregnant rats treated with saline), Norm-Preg+Nebivolol (sham-operated pregnant rats treated with nebivolol), RUPP (pregnant rats submitted to the RUPP model and treated with saline) and RUPP+Nebivolol (RUPP rats treated with nebivolol). The main hypothesis is that nebivolol attenuates hypertension and endothelial dysfunction and increases the bioavailability of nitric oxide in preeclampsia.