Cardiovascular regulation in mice with attenuation or overexpression of the gene of vesicular acetylcholine transporter (VAChT): parasympathetic function in heart failure

• Grant number: 14/01089-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 20, 2014
• End date: December 19, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: GEISA CRISTINA SINGOLANI VACCARI TEZINI REIS
• Supervisor: Marco A. M. Prado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Western University , Canada
• Associated to the scholarship: 13/06452-0 - CARDIOVASCULAR REGULATION IN MICE WITH ATTENUATION OR OVEREXPRESSION OF THE GENE OF VESICULAR ACETYLCHOLINE TRANSPORTER (VAChT): PARASYMPATHETIC FUNCTION IN HEART FAILURE., BP.PD

Abstract

The literature shows scarce information concerning the parasympathetic participation in the maintenance of cardiovascular function in heart failure (Olshansky et al., 2008; Sabbah, 2012). Studies have shown that a parasympathetic hypoactivity has been identified as an independent risk factor in patients with myocardial infarction (Kleiger et al., 1987; La Rovere et al., 1998). Therefore, this study aims to evaluate, in genetically modified mice, the effects of the attenuation or the overexpression of the gene of vesicular acetylcholine transporter (VAChT) on the hemodynamic parameters (arterial pressure and heart rate) and sympathovagal balance upon cardiovascular regulation. In addition, it will be also examined the cardiovascular responses of genetically modified mice during the development of heart failure (HF). Mice will be assigned into three groups: Wild-type (WT); knockdown homozygous for the gene of vesicular acetylcholine transporter (VAChT KDHOM); and with overexpression of the gene of vesicular acetylcholine transporter (ChAT-ChR2-EYFP). The animals will be implanted chronically with telemetry probe for hemodynamic characterization and sympathovagal balance evaluation. Next, the mice will be submitted to the development of HF by left coronary artery ligation to elicit myocardial infarction. Assessment of the autonomic function will be conducted throughout the following approaches: 1) cardiac sympathovagal balance will be measured by the administration of methylatropine and propranolol; 2) heart rate and arterial pressure variability will be evaluated in the time and frequency domain (spectral analysis); 3) analysis of baroreflex sensitivity by the Sequence Method. All animals will be subjected to the analysis of cardiac function by echocardiography. At the end of the protocols the hearts will be examined by means of histology. (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)

DURAND, MARINA T.; BECARI, CHRISTIANE; TEZINI, GEISA C. S. V.; FAZAN, JR., RUBENS; OLIVEIRA, MAURO; GUATIMOSIM, SILVIA; PRADO, VANIA F.; PRADO, MARCO A. M.; SALGADO, HELIO C.. Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 4, p. H655-H662, AUG 15 2015. (13/20549-7, 14/01089-8, 13/06452-0)