Evaluation of the proton pump inhibitor effects on blood pressure, vascular function and nitric oxide bioavailability in gestational hypertension in rats

• Grant number: 21/08380-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Carlos Alan Candido Dias Junior
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia (PE) is a disease that occurs in pregnancy and is characterized by elevated maternal blood pressure accompanied by endothelial dysfunction. Its pathogenesis is still not well understood; however, placental ischemia and hypoxia has shown importance in pathophysiology. In PE there is an increase in oxidative stress, increases in antiangiogenic factors and decreases in vasodilator mediators, such as nitric oxide (NO). Studies show that proton pump inhibitors (PPIs) may compromise the bioavailability of NO in a pH-dependent manner and also reduce NO synthesis by inhibiting the activity of the enzyme DDAH (dimethylarginine dimethylaminohydrolase) that metabolizes ADMA (asymmetric dimethylarginine), which is an endogenous inhibitor of NO synthase (NOS). Thus, PPIs commonly used by pregnant women to relieve symptoms of gastric reflux may compromise the bioavailability of NO; however, these actions of PPIs are not elucidated in pregnancy as well as in gestational hypertension and PE. Therefore, in the present project we will use the experimental model of gestational hypertension and PE induced by RUPP, which consists of reduced uterine perfusion pressure and that has been shown to be very promising for mimicking pathophysiological responses found in human PE. Our main hypothesis is that the impairment of NO bioavailability caused by PPI will aggravate gestational hypertension. In addition, we will also evaluate markers of angiogenesis (sFlt-1, soluble fms-like tyrosine kinase-1) and PLGF (Placental Growth Factor) as well as DDHA and ADMA in this experimental model. This study evaluates the impact of the use of PPI on the bioavailability of NO in gestational hypertension experimentally induced. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RODRIGUES, SERGINARA DAVID; DA SILVA, MARIA LUIZA SANTOS; MARTINS, LAISLA ZANETONI; GOMES, SASKIA ESTELA BIASOTTI; MARIANI, NOEMIA A. P.; SILVA, ERICK J. R.; KUSHIMA, HELIO; MATTOS, BRUNA RAHAL; RIZZI, ELEN; DIAS-JUNIOR, CARLOS ALAN. Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide. Life Sciences, v. 331, p. 13-pg., 2023-10-15. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)

MARTINS, LAISLA ZANETONI; DA SILVA, MARIA LUIZA SANTOS; RODRIGUES, SERGINARA DAVID; GOMES, SASKIA ESTELA BIASOTTI; MOLEZINI, LAURA; RIZZI, ELEN; MONTENEGRO, MARCELO FREITAS; DIAS-JUNIOR, CARLOS ALAN. Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 16, p. 16-pg., 2023-08-01. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)