Cardiovascular and metabolic responses to electrical vagal nerve stimulation in rodents

• Grant number: 13/19127-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): January 01, 2014
• Effective date (End): May 31, 2014
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Helio Cesar Salgado
• Grantee: Daniel Penteado Martins Dias
• Supervisor: Harald Martin Stauss
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Iowa, United States
• Associated to the scholarship: 12/16121-9 - Cardiovascular and Metabolic Responses to Electrical Vagal Nerve Stimulation in Rodents, BP.PD

Abstract

The central nervous system (CNS) reflexively controls the autonomic efferent activity to the cardiovascular system, contributing to the maintenance of cardiovascular homeostasis. Among several mechanisms involved in the control of the cardiovascular system, we can highlight the baroreceptor reflex. The baroreflex consists of an afferent portion, central integration and efferent pathways that play a crucial role in regulating arterial blood pressure (BP). Several techniques have been used in the assessment of the cardiovascular autonomic modulation (CAM). Among them, we can mention the electrical stimulation and activity recording of neural pathways. Studies from the 60's indicate that the electrical stimulation of baroreceptors decreases BP in hypertensive patients resistant to antihypertensive drug therapy. In our laboratory, the electrical stimulation of baroreceptor afferent pathways has been successfully used to evaluate the CAM under physiological and pathophysiological (hypertension) conditions. Over the past years, the prevalence of cardiovascular disease (CVD) has substantially increased and obesity seems to be closely related to the occurrence of CVD. Several strategies can be used in obesity management, such as: reduction in caloric intake, increase in energy expenditure, bariatric surgeries, among others. The electrical stimulation of the vagus nerve (VNS) in epileptic patients resistant to conventional treatment, as well as in depressive patients, promotes parallel reduction in body weight. The vagus nerve contains fibers that carry information between the CNS and organs in the thoracic and abdominal cavities. Following activation of sensory endings, the vagal afferents transmit information to the CNS modulating food intake. Despite evidences showing that the VNS is a promising technique, VNS parameters are not well established yet. Technological advances have allowed the use of miniaturized probes (microchips) for VNS. These devices permit fine-tuning of the parameters and, occasionally, the adjustment of parameters even with the device already implanted. In the current study, we aim to develop a miniaturized probe for VNS in rats, which may be customized for electrical stimulation of other neural pathways in upcoming studies. Additionally, the study aims to identify VNS parameters that promote metabolic changes with slight effects on cardiovascular function. The project will be developed in close collaboration with well-recognized researchers from the University of Iowa (Iowa City, IA, USA). The study aims to evaluate the behavioral, metabolic and cardiovascular responses of control and obese male Sprague Dawley rats subjected to VNS. The animals will be subjected to conventional or hyperlipidemic diet during 2 weeks and then instrumented with probes for VNS and BP recording (telemetry). Following 2 weeks of VNS, the rats will be anesthetized and implanted with a catheter into the femoral vein. Finally, a post-surgical recovery period will be allowed and rats will be subjected to the experimental protocol for evaluation of behavioral (depressive behavior), metabolic (basal metabolic rate) and cardiovascular (BP, heart rate, cardiovascular variability, baroreflex sensitivity and CAM) parameters. In the current study, it is hoped that the VNS promotes metabolic changes without significant effects on cardiovascular parameters. In addition, we expect that the development of miniaturized probes (microchips) for VNS contribute to future studies in which the electrical stimulation of neural pathways is used for assessment of cardiovascular control mechanisms. (AU)