Effects of chronic electrical stimulation of carotid sinus in cardiovascular function in spontaneously hypertensive rats

• Grant number: 13/13269-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2013
• Effective date (End): June 30, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rubens Fazan Junior
• Grantee: Gean Domingos da Silva Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Essential hypertension affects about 35% of the population above 40 years of age and is strongly associated with increased risk of serious cardiovascular events. Hypertension affects various organs such as the heart, blood vessels, and kidneys, as well as affects cardiovascular autonomic modulation leading to sympathetic hyperactivity and reduced vagal parasympathetic drive to the heart. Clinical evidence has demonstrated that hypertension is associated with increased plasma concentrations of inflammatory mediators, and also with vascular inflammation. The increase in the number of circulating lymphocytes and monocytes, overproduction of cell adhesion molecules and inflammatory cytokines such as tumor necrosis factor ± (TNF-±), interleukin-6 (IL-6) and C-reactive protein characterize the inflammatory process in arterial hypertension. Such changes are also observed in spontaneously hypertensive rats (SHR). On the other hand, intracerebroventricular infusion of IL-1² a proinflammatory cytokine, activates the sympathetic and produces increased blood pressure (BP).The stimulation of vagal afferents by cytokines and other products of inflammation triggers anti-systemic inflammatory responses mediated by the hypothalamic-pituitary adrenal axis. However, the efferent activity (parasympathetic) of the vagus also exerts a marked anti-inflammatory effect, featuring what is called inflammatory reflex which targets the spleen and other organs that produce cytokines, where expression is inhibited by these molecular mechanisms mediated by receptor nicotinic acetylcholine type ±-7 (±-7nAChR). Much attention has been given to the potential use of electrical stimulation of the vagus nerve as a tool of anti-inflammatory action, which has been shown to be safe and effective in treating various diseases such as Alzheimer's disease, neuropathic pain, traumatic injuries of the brain, and also in protect the brain against ischemic injury.The arterial baroreflex is a major mechanism of short-term BP regulation, producing significant sympathetic inhibition and parasympathetic stimulation. Electrical stimulation of baroreceptor afferent nerve in rats with different objectives, is a technique used in the 60' s as an approach to treat hypertension in view of the limitations of pharmacological therapy at the time. However, currently the electrical stimulation of the carotid sinus is again being used as a method to treat refractory hypertension.Therefore, this project aims to evaluate the influence of chronic electrical stimulation of the carotid sinus (carotid baroreceptors) on inflammatory and cardiovascular changes in SHR. Will be analyzed in young adult SHR, hemodynamic parameters (BP, HR and cardiac function), autonomic (sympathetic and vagal tone), inflammatory (circulating cytokines), and the injury of target organs: heart (cardiac remodeling) and blood vessels (expression cell adhesion molecules, mediators of regulatory T lymphocytes, endothelial function and vascular remodelling).

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)

SANTOS-ALMEIDA, FERNANDA MACHADO; DOMINGOS-SOUZA, GEAN; MESCHIARI, CESAR A.; FAVARO, LAURA CAMPOS; BECARI, CHRISTIANE; CASTANIA, JACI A.; LOPES, ALEXANDRE; CUNHA, THIAGO M.; MORAES, DAVI J. A.; CUNHA, FERNANDO Q.; et al. Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation. SCIENTIFIC REPORTS, v. 7, JUL 24 2017. (13/06452-0, 13/20549-7, 11/20343-4, 13/26217-6, 13/13269-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Gean Domingos da Silva. Cardiovascular responses to electrical stimulation of carotid sinus in conscious normotensive and Hypertensive rats (SHR). 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.