Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental Hypertension and Obesity

• Grant number: 16/23513-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2016
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Débora Simões de Almeida Colombari
• Grantee: Marlusa Karlen Amarante
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 15/23467-7 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental hypertension and obesity, AP.TEM
• Associated scholarship(s): 19/11696-2 - Participation of respiratory oscillators on the modulation of RVLM presympathetic neurons in offspring from obese dams, BE.EP.PD

Abstract

Obesity and Hypertension are the leading cause of death in the world. Obesity and overweight contribute to elevated blood pressure in many patients with essential Hypertension. Experimental and clinical studies indicate that visceral obesity induces hypertension by increasing renal sodium reabsorption through multiple mechanisms including activation of the Sympathetic Nervous System (SNS). Obesity-related Hypertension is associated with altered responsiveness of SNS and the Renin-Angiotensin-System (RAS), possibly leading to blunted sympatho-inhibitory and vasodilator effects in the renal and splanchnic vasodilator beds. The present Thematic Project aims to understand the neural mechanisms that process such neuroautonomic information associates to the cardiovascular and respiratory adjustments during the development of hypertension in different experimental models. The main focus of this study is a model of circuit that involves the triangle formed for rhomboencephalic regions, nucleus of the solitary tract (NTS), rostro-ventrolateral region of the medulla (RVLM) and its connections with prosencephalic regions like lamina terminalis and paraventricular nucleus of the hypothalamus. The objectives of the project are: 1) to study the involvement of the RAS and the melanocortin system on the cardiovascular and ventilatory responses to Obesity; 2) to study the neural mechanisms involved in the changes of SNS and respiration induced by modifications in the dietary nutrients during the development and maturation (Epigenetic); 3) To test if moderate intensity resistance training prevents the alterations in blood pressure, sympathetic modulation of systolic blood pressure and baroreflex function in high-fat diet feeding rats. In addition, it will be also tested if the positive effects on cardiovascular system induced by resistance training are accompanied by the prevention of alterations in RAS and cytokines mRNA expression within the NTS; 4) to verify the participation of the oxidative stress (ROS) in different encephalic areas during the development and maintenance of renovascular Hypertension (2-kidneys, 1-clip, 2R1C) and essential Hypertension (spontaneously hypertensive rats, SHR); 5) to study the involvement of the central RAS and inflammatory cytokines in the central nervous system as a possible facilitator mechanism for the development of different models of hypertension (2R1C, and SHR, and that induced by obesity). To reach these objectives the project will combine different techniques such as: central injections of drugs; viral transfection; imunohystochemistry; analysis of the quantitative gene expression, electrophysiology; cardiovascular and ventilatory measurements. The purpose is to deal with two important questions: 1) which are the central pathways activated to induce hypertension and ventilatory alterations in the different models of Hypertension?; 2) which are the mechanisms activated in these central pathways to induce increase in the arterial pressure and alterations in the ventilation in rats in the different models of Hypertension? The neuronal pathways and cell signalling mechanisms that permit selective control of SNS activity and cardio-respiratory adaptation independent or not from RAS and ROS activation are still unclear and remain an important area for research, especially considering the current worldwide epidemic Hypertension and Obesity and its adverse impact on human health. (AU)

Scientific publications

(4)

(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)

KARLEN-AMARANTE, MARLUSA; HUFF, ALYSSA; BAERTSCH, NATHAN; COLOMBARI, DEBORA; RAMIREZ, JAN-MARINO. Optogenetic stimulation of Dbx1 neurons promote increas in sympathetic activity in vivo. FASEB JOURNAL, v. 34, p. 2-pg., 2020-04-01. (16/23513-1)

RAMIREZ, JAN-MARINO; KARLEN-AMARANTE, MARLUSA; WANG, JIA-DER JU; BUSH, NICHOLAS E.; CARROLL, MICHAEL S.; WEESE-MAYER, DEBRA E.; HUFF, ALYSSA. The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions. PHYSIOLOGY, v. 35, n. 6, p. 375-390, NOV 2020. (16/23513-1, 19/11696-2)

KARLEN-AMARANTE, MARLUSA; ZOCCAL, DANIEL B.; MENANI, JOSE V.; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.. OFFSPRING OF OBESE DAMS PRESENT CHANGES IN RESPIRATORY AND SYMPATHETIC ACTIVITIES. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (13/17251-6, 16/23513-1)

KARLEN-AMARANTE, MARLUSA; HUFF, ALYSSA; BAERTSCH, NATHAN; COLOMBARI, DEBORA; RAMIREZ, JAN-MARINO. Optogenetic stimulation of Dbx1 neurons enhances the respiratory-sympathetic coupling in in vivo CIH mice. FASEB JOURNAL, v. 35, p. 1-pg., 2021-05-01. (16/23513-1)