Modulation of the inflammatory response to LPS by electrical activation of the baroreflex in conscious rats

• Grant number: 14/15386-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2014
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Fernanda Brognara Penteado Dias
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The nervous system can modulate systemic inflammatory responses to a wide variety of stressors. Currently, emphasis has been given to the role played by the vagus nerve in modulating immune responses of the body. Vagal activation plays an important role in the inflammatory reflex inhibiting the innate immune response, reducing the release of pro-inflammatory cytokines in the spleen, through an alfa-7 nicotinic acetylcholine receptor (alfa7nAChR) dependent mechanism. The arterial baroreflex inhibits sympathetic outflow and increases parasympathetic activity to the heart. Thus, activation of baroreceptors (arterial baroreflex afferent) can shift the sympathovagal balance towards the parasympathetic side; and possibly modulate the inflammatory response through the inflammatory reflex. In rats, the electrical stimulation of the aortic depressor nerve (ADN) has been regularly used in our laboratory for activation of the baroreflex. Objective: The study aims to examine the influence of electrical stimulation of the ADN on cardiovascular and inflammatory changes observed following LPS-induced endotoxemia in rats. Methods: Wistar rats will be assigned to 4 groups: 1) electrical stimulation of the ADN plus LPS administration; 2) LPS administration alone; 3) electrical stimulation of the ADN plus saline administration; 4) saline administration alone. Rats will be anesthetized and the ADN will be isolated and implanted with a bipolar electrode and the femoral artery and the jugular vein will be implanted with catheters. The ends of the electrodes and the vascular catheters will be exteriorized at the dorsal part of the neck. Control animals will be subjected to similar procedures, but will not have electrodes implanted into the ADN. On next day, conscious animals will have the femoral catheter connected to a pressure transducer and the electrodes connected to an electric stimulator. The experimental protocol consists of a baseline recording of hemodynamic parameters (30 min) followed by administration of LPS (1.5 mg/kg, i.v.) or saline (0.05 mL/100g, i.v.). Next, electrical stimulation (15 Hz; 0.25 ms; 0.5 mA) of the ADN will be applied for 60 min. As electrical stimulation ceases, a blood sample (1 mL) will be collected through the catheter into the femoral artery, followed by infusion of a volume of saline equal to the blood sample taken. Two and three hours after administration of saline or LPS, rats will have the blood pressure and heart rate sampled for 10 minutes, followed by blood sample collection. Quantitation of levels of cytokines in plasma will be carried out. At the end of the protocol the animals will be subjected to decapitation - guillotine - and organs will be collected (heart, spleen, and hypothalamus), frozen and used for the analysis of tissue cytokines. (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)

BROGNARA, FERNANDA; CASTANIA, JACI A.; DIAS, DANIEL P. M.; LOPES, ALEXANDRE H.; FAZAN, JR., RUBENS; KANASHIRO, ALEXANDRE; ULLOA, LUIS; SALGADO, HELIO C.. Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats. Brain Research, v. 1682, p. 54-60, MAR 1 2018. (14/15386-4, 11/20343-4, 13/20549-7, 17/05163-6)

BASSI, GABRIEL S.; BROGNARA, FERNANDA; CASTANIA, JACI A.; TALBOT, JHIMMY; CUNHA, THIAGO M.; CUNHA, FERNANDO Q.; ULLOA, LUIS; KANASHIRO, ALEXANDRE; MARTINS DIAS, DANIEL P.; SALGADO, HELIO C.. Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function. BRAIN BEHAVIOR AND IMMUNITY, v. 49, p. 140-147, OCT 2015. (14/15386-4, 13/20549-7, 13/08216-2, 11/20343-4, 12/04237-2)

BROGNARA, FERNANDA; MARTINS DIAS, DANIEL P.; CASTANIA, JACI A.; FAZAN, JR., RUBENS; LEWIS, STEPHEN J.; SALGADO, HELIO C.. Cardiovascular responses elicited by continuous versus intermittent electrical stimulation of the aortic depressor nerve in conscious rats. Life Sciences, v. 148, p. 99-105, MAR 1 2016. (14/15386-4, 13/20549-7)