Evaluation in vitro and in vivo of 6-nitrodopamine in a non-reperfused myocardial infarction and its association with reactive oxygen species in mice

• Grant number: 24/14880-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 15, 2025
• End date: December 14, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Vivian Fuguhara de Lima
• Supervisor: Ruhul Abid
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Brown University, United States
• Associated to the scholarship: 22/07737-8 - Evaluation of the cardiovascular effect of 6-nitrodopamine in isolated atrium and perfused rat heart, BP.DD

Abstract

6-nitrodopamine (6-ND) is a novel catecholamine with significant role as a cardiovascular mediator. In the hypertension model with N¿-nitro-L-arginine methyl ester (L-NAME), the chronic treatment with 6-ND prevented the hypertension and heart lesions. In addition, previous studies showed that its basal release is increased with hydrogen peroxide, superoxide dismutase, and decreased with catalase. Prof. Ruhul Abid research group from Brown University, Providence (USA), developed a transgenic model that overexpresses (OE) mitochondrial antioxidant MnSOD (MnSOD-OE), a superoxide dismutases that converts superoxide anion (O2-) into H2O2. Thus, this project aims to investigate the association of 6-ND with the reactive oxygen species (ROS), and the chronic effect of 6-ND in the infarction size by permanent left anterior descending coronary artery (LAD) ligation surgery. The experiments will be performed in control mice, in which before the non-reperfused myocardium infarct (MI) induction, osmotic mini-pumps with saline, 6-ND 6 nmoles/day or 60 nmoles/day are going to be implanted for 28 days of treatment. Histological analysis will be used to evaluate the effect of 6-ND in the infarct size and collagen deposit. Furthermore, along with the animals with MI, the transgenic model MnSOD-OE is also going to be used to quantify the basal release of 6-nitrodopamine and other novel catecholamines in tissues from the cardiovascular, endocrine, gastrointestinal, respiratory, urogenital and nervous system by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).