Evaluation of the impact of preeclampsia induced by NOS inhibition on AVP-producing neurons in pregnant mice

• Grant number: 22/07286-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2022
• End date: December 31, 2022
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Andre de Souza Mecawi
• Grantee: Marcelo Henrique Santos de Carvalho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/27581-0 - Control of vasopressin secretion in pregnancy and its implications in pathophysiology of Preeclampsia, AP.JP

Abstract

Pregnancy is a period of extreme changes in the female's physiology, adapting the mother's organism to ensure the healthy development of the embryo/fetus. Preeclampsia (PE) is a disease characteristic of pregnancy and defined by the development of hypertension in the second half of pregnancy, associated with proteinuria and/or end-organ dysfunction. It affects between 3 and 5% of pregnant women in the world and 8% in the poorest regions of Brazil, being one of the main causes of maternal and fetal death. It has long been known that there is a reduction in the osmotic threshold for activating vasopressin-producing neurons (AVP) during pregnancy, but it was only in this decade that the hypersecretion of this vasoactive hormone was implicated in the induction of PE. Despite this recent finding, the mechanisms responsible for the increased secretion of AVP and consequent induction of PE are not known. The general objective of this project is to study the mechanisms responsible for altering the osmosensitivity of AVP-producing neurons during pregnancy, as well as to understand the consequences of its hypersecretion for the development of PE. Using the preclinical model of preeclampsia induced by the inhibition of the enzyme nitric oxide synthase (NOS) with L-NAME in drinking water, we will study the molecular and functional alterations of AVP-producing magnocellular neurons in normal and pre-eclamptic pregnancy. . We hope, therefore, to contribute to the understanding of changes in AVP secretion during pregnancy and its implication in the induction of PE, enabling the development of new strategies for the prevention, diagnosis, and treatment of this disease.(AU)