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

• Grant number: 15/23467-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2016
• End date: February 28, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Eduardo Colombari
• Grantee: Eduardo Colombari
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Pesquisadores principais: Débora Simões de Almeida Colombari ; José Vanderlei Menani
• Associated research grant(s): 18/23157-6 - Central nervous system sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline and/or hypertonic potassium solution in awake rats, AV.EXT; 18/04134-5 - Genetic identity and neural circuit connections of aldosterone-sensitive neurons in rat and mouse NTS, AV.EXT; 17/15886-5 - Participation of the nucleus of the commissural solitary tract and carotid corpuscles during the development and maintenance of renovascular hypertension in rats, AV.EXT
• Associated scholarship(s): 21/08447-0 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental Hypertension and Obesity, BP.PD; 20/05045-6 - Control of breathing pattern: interactions between respiratory oscillators, BP.DR; 20/10180-0 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental Hypertension and Obesity, BP.PD; + associated scholarships 19/22767-8 - Mechanisms involved in the cardiovascular and hydroelectrolytic changes induced by central Angiotensin II and osmoreceptors in rats fed with a high-fat diet, BP.DR; 19/19164-0 - Cardiovascular changes and neuronal activation induced by furosemide associated with captopril in rats fed with a high-fat diet, BP.IC; 19/11196-0 - Mechanisms and neural circuits involved in the interaction between peripheral inflammation and sympathoexcitation in Renovascular Hypertension, BP.PD; 18/02194-0 - Role of central aldosterone in the neural control of renal function, BP.MS; 17/10762-6 - Cardiovascular changes induced by high fat diet: possible role of forebrain mechanisms, BP.MS; 17/04649-2 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental hypertension and obesity, BP.PD; 16/23513-1 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental Hypertension and Obesity, BP.PD - associated scholarships

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

(23)

(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)

LAUAR, MARIANA R.; BLANCH, GRAZIELA T.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; DE PAULA, PATRICIA M.; DE LUCA JR, LAURIVAL A.; MENANI, V, JOSE. Anti-hypertensive effect of hydrogen peroxide acting centrally. HYPERTENSION RESEARCH, MAY 2020. (13/05189-4, 15/23467-7)

DA SILVA, ELAINE FERNANDA; BASSI, MIRIAN; MENANI, JOSE VANDERLEI; ALMEIDA COLOMBARI, DEBORA SIMOES; ZOCCAL, DANIEL BRESEGHELLO; PEDRINO, GUSTAVO RODRIGUES; COLOMBARI, EDUARDO. Carotid bodies contribute to sympathoexcitation induced by acute salt overload. Experimental Physiology, v. 104, n. 1, p. 15-27, JAN 2019. (11/50770-1, 13/17251-6, 15/23467-7)

MELO, MARIANA ROSSO; GASPARINI, SILVIA; SPERETTA, GUILHERME F.; SILVA, ELAINE FERNANDA; PEDRINO, GUSTAVO RODRIGUES; MENANI, V, JOSE; ZOCCAL, DANIEL B.; ALMEIDA COLOMBARI, DEBORA SIMOES; COLOMBARI, EDUARDO. Importance of the commissural nucleus of the solitary tract in renovascular hypertension. HYPERTENSION RESEARCH, v. 42, n. 5, p. 587-597, MAY 2019. (14/01159-6, 13/17251-6, 15/23467-7)

BARBOSA, RAFAELA MOREIRA; SPERETTA, GUILHERME F.; MARTINS DIAS, DANIEL PENTEADO; RUCHAYA, PRASHANT JAY; LI, HONGWEI; MENANI, JOSE VANDERLEI; SUMNERS, COLIN; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.. Increased Expression of Macrophage Migration Inhibitory Factor in the Nucleus of the Solitary Tract Attenuates Renovascular Hypertension in Rats. AMERICAN JOURNAL OF HYPERTENSION, v. 30, n. 4, p. 435-443, APR 2017. (15/23467-7, 11/50770-1)

DA SILVA, ELAINE FERNANDA; SOARES DE MELO, ARYANNE BATISTA; LOBO JUNIOR, EULICIO DE OLIVEIRA; RODRIGUES, KARLA LIMA; NAVES, LARA MARQUES; TOMAZELLI COLTRO, WENDELL KARLOS; SILVA REBELO, ANA CRISTINA; FREIRIA-OLIVEIRA, ANDRE HENRIQUE; MENANI, JOSE VANDERLEI; PEDRINO, GUSTAVO RODRIGUES; et al. Role of the Carotid Bodies in the Hypertensive and Natriuretic Responses to NaCl Load in Conscious Rats. FRONTIERS IN PHYSIOLOGY, v. 9, DEC 4 2018. (15/23467-7)

ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; FLOR, KARINE C.; DA SILVA, MELINA P.; COSTA-SILVA, JOAO H.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; MURPHY, DAVID; PATON, JULIAN F. R.. Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats. Experimental Physiology, v. 104, n. 9, p. 1371-1383, SEP 2019. (13/06077-5, 15/23467-7, 13/10484-5)

ZENATTI, A. A.; PEREIRA JR, E. D.; POSSARI, J.; ANDRADE, C. A. F.; MENANI, V, J.; DE LUCA JR, L. A.. Interference with the renin-angiotensin system reduces the palatability of 0.3 M NaCl in sodium-deplete rats. APPETITE, v. 158, MAR 1 2021. (15/23467-7, 11/50770-1, 19/01220-0, 15/20500-3)

MELO, MARIANA ROSSO; VOGER, JOSHUA J.; CONNELLY, ANGELA A.; BASSI, JASPREET K.; COLOMBARI, EDUARDO; ALLEN, ANDREW M.. Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats. Neuroscience Letters, v. 787, p. 6-pg., 2022-07-30. (15/23467-7, 16/02091-1, 14/01159-6, 13/17251-6)

KATAYAMA, PEDRO L.; LEIRAO, ISABELA P.; KANASHIRO, ALEXANDRE; LUIZ, JOAO P. M.; CUNHA, FERNANDO Q.; NAVEGANTES, LUIZ C. C.; V. MENANI, JOSE; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO. The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex. BRAIN BEHAVIOR AND IMMUNITY, v. 102, p. 17-pg., 2022-03-25. (19/11196-0, 15/23467-7)

KATAYAMA, PEDRO L.; LEIRAO, ISABELA P.; KANASHIRO, ALEXANDRE; MENANI, JOSE, V; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO. The carotid body: A novel key player in neuroimmune interactions. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., 2022-10-24. (19/11196-0, 19/24154-3, 15/23467-7)

LAUAR, MARIANA R.; COLOMBARI, DEBORA S. A.; DE PAULA, PATRICIA M.; COLOMBARI, EDUARDO; ANDRADE, CARINA A. F.; DE LUCA JR, LAURIVAL A.; MENANI, JOSE V.. Chronic administration of catalase inhibitor attenuates hypertension in renovascular hypertensive rats. Life Sciences, v. 319, p. 11-pg., 2023-03-07. (15/23467-7, 13/05189-4)

DE MELO, MARIANA DEL ROSSO; GASPARINI, SILVIA; SILVA, ELAINE FERNANDA; KARLEN-AMARANTE, MARLUSA; SPERETTA, GUILHERME F. F.; LAUAR, MARIANA RUIZ; PEDRINO, GUSTAVO; MENANI, JOSE VANDERLEI; COLOMBARI, DEBORA S. A.; ZOCCAL, DANIEL B.; et al. Excitatory Inputs from Carotid Bodies Drive Respiratory Changes in Renovascular Hypertensive Rats. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (14/01159-6, 15/23467-7)

GASPARINI, S.; MELO, M. R.; LEITE, G. F.; NASCIMENTO, P. A.; ANDRADE-FRANZE, G. M. F.; MENANI, J. V.; COLOMBARI, E.. RAPID STIMULATION OF SODIUM INTAKE COMBINING ALDOSTERONE INTO THE 4TH VENTRICLE AND THE BLOCKADE OF THE LATERAL PARABRACHIAL NUCLEUS. Neuroscience, v. 346, p. 94-101, MAR 27 2017. (13/00026-0, 15/23467-7, 11/50770-1)

GASPARINI, S.; MELO, M. R.; ANDRADE-FRANZE, G. M. F.; GEERLING, J. C.; MENANI, J. V.; COLOMBARI, E.. Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes. Brain Research, v. 1698, p. 70-80, NOV 1 2018. (13/00026-0, 15/23467-7, 18/04134-5)

AMARAL, NATHALIA ODA; BASSI, MIRIAN; SA, JESSICA M.; BARBOSA, RAFAELA MOREIRA; ZOCCAL, DANIEL; MENANI, JOSE; COLOMBARI, EDUARDO; PEDRINO, GUSTAVO; ALMEIDA COLOMBARI, DEBORA SIMOES. Sympathetic and phrenic nerve activities in the offspring of high fat diet feeding dams. FASEB JOURNAL, v. 31, p. 1-pg., 2017-04-01. (15/23467-7)

LAUAR, MARIANA R.; BLANCH, GRAZIELA T.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; DE PAULA, PATRICIA M.; DE LUCA JR, LAURIVAL A.; MENANI, JOSE, V. Anti-hypertensive effect of hydrogen peroxide acting centrally. HYPERTENSION RESEARCH, v. 43, n. 11, p. 12-pg., 2020-05-27. (15/23467-7, 13/05189-4)

SILVA, ELAINE; NAKAI, LARISSA; ALEXANDRE PATRONE, LUIS; GARGAGLIONI, LUCIANE; MENANI, JOSE; ALMEIDA COLOMBARI, DEBORA; ZOCCAL, DANIEL; COLOMBARI, EDUARDO. Water Deprivation Enhances the Late Expiratory Activity of Abdominal Nerve During Hypercapnia and Hypoxia in Rats. FASEB JOURNAL, v. 34, p. 2-pg., 2020-04-01. (15/23467-7, 17/04649-2)

DE MELO, MARIANA DEL ROSSO; ONG, SARAH J. M.; CONNELLY, ANGELA A.; BASSI, JASPREET K.; COLOMBARI, EDUARDO; ALLEN, ANDREW M.. Involvement of Phox2B Neurons Located in the Commissural NTs with the Maintenance of Hypertension in SH Rats. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (16/02091-1, 15/23467-7)

MELO, MARIANA ROSSO; GASPARINI, SILVIA; SILVA, ELAINE F.; KARLEN-AMARANTE, MARLUSA; SPERETTA, GUILHERME F.; LAUAR, MARIANA R.; PEDRINO, GUSTAVO R.; MENANI, V, JOSE; COLOMBARI, DEBORA S. A.; ZOCCAL, DANIEL B.; et al. Renovascular hypertension elevates pulmonary ventilation in rats by carotid body-dependent mechanisms. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 318, n. 4, p. R730-R742, APR 2020. (14/01159-6, 15/23467-7)

RONCARI, CAMILA F.; BARBOSA, RAFAELA M.; VENDRAMINI, REGINA C.; DE LUCA, JR., LAURIVAL A.; MENANI, JOSE V.; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.. Enhanced angiotensin II induced sodium appetite in renovascular hypertensive rats. Peptides, v. 101, p. 82-88, MAR 2018. (15/23467-7, 11/50770-1)

FERNANDES, MARCOS VINICIUS; MELO, MARIANA ROSSO; MOWRY, FRANCESCA ELISABETH; LUCERA, GABRIELA MARIA; LAUAR, MARIANA RUIZ; FRIGIERI, GUSTAVO; BIANCARDI, VINICIA CAMPANA; MENANI, V, JOSE; ALMEIDA COLOMBARI, DEBORA SIMOES; COLOMBARI, EDUARDO. Intracranial Pressure During the Development of Renovascular Hypertension. Hypertension, v. 77, n. 4, p. 1311-1322, APR 2021. (15/23467-7)

FAZAN, FREDERICO; COLOMBARI, DEBORA SIMOES DE ALMEIDA; MENANI, JOSE VANDERLEI; FAZAN, JR., RUBENS; COLOMBARI, EDUARDO. Electrocardiographic changes in the acute hyperkalaemia produced by intragastric KCl load in rats. Experimental Physiology, v. 106, n. 5, MAR 2021. (18/02194-0, 15/23467-7)

MOREIRA, THIAGO S.; TAKAKURA, ANA C.; COLOMBARI, EDUARDO. Editorial: Integrative Physiology: Systemic Hypertension and Respiratory-Sympathetic Coupling. FRONTIERS IN PHYSIOLOGY, v. 13, p. 3-pg., 2022-01-26. (15/23376-1, 15/23467-7, 19/01236-4)