New insights in cardiovascular regulation under physiological and pathophysiological condition

• Grant number: 13/20549-7
• Support Opportunities: Research Projects - Thematic Grants
• Duration: November 01, 2014 - October 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Helio Cesar Salgado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Rubens Fazan Junior ; Valéria Paula Sassoli Fazan
• Associated researchers: Christiane Becari ; Daniel Penteado Martins Dias ; Geisa Cristina Singolani Vaccari Tezini Reis ; Lindolfo da Silva Meirelles ; Marco Antonio Maximo Prado ; Renata Maria Lataro ; Silvia Carolina Guatimosim Fonseca
• Associated grant(s): 18/04263-0 - 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, AR.EXT
• Associated scholarship(s): 20/08221-0 - Role of electrical activation of the carotid sinus nerve in the inflammatory response elicited by colitis, BP.IC; 20/08312-5 - Effect of sympathetic inhibition and vagal activation on inflammatory mediators in endotoxemic rats, BP.IC; 18/20939-3 - New insights in Cardiovascular Regulation under Physiological and Pathophysiological Condition., BP.PD; + associated scholarships 18/10455-9 - Role of electrical activaton of the carotid sinus nerve, in conscious rats, in the attenuation of local and systemic inflammatory response elicited by periodontitis., BP.PD; 17/02537-2 - Effects of ivabradine on myocardial ischemia and reperfusion injury in rats, BP.IC; 17/05163-6 - Role of the parasympathetic and sympathetic autonomic nervous system in the modulation of sepsis in unanesthetized rats, BP.DD; 16/19089-0 - Comparison between two techniques for heart failure induction in rats: permanent coronary artery ligation and ischaemia-reperfusion, BP.IC; 15/21976-1 - Cardiovascular autonomic control in toll-like receptor 9 knockout mice with hypertension induced by angiotensin II., BP.PD; 15/20463-0 - New insights in cardiovascular regulation under physiological and pathophysiological condition, BP.PD; 15/26621-7 - New insights in cardiovascular regulation under physiological and pathophysiological condition, BP.IC; 15/18511-7 - Role of carotid chemoreceptors in hemodynamic and ventilatory responses to electrical stimulation of the carotid sinus and effects of its chronic inhibition in the development of hypertension in Spontaneously Hypertensive Rats (SHR), BP.DD - associated scholarships

Abstract

The present study was grouped into five Projects investigating the cardiovascular regulation under physiological - Project 1 - and physiopathological - heart failure (HF) - condition, i.e. Project 2, 3, 4A e 4B.Project 1 aims to characterize the presence of substance P in the axons of the aortic depressor nerve (ADN) and nodose ganglion. To accomplish this, it will be used immunohistochemical staining, Western Blotting and expression of mRNA by means of Real Time-PCR. The technique for staining substance P from unmyelinated fibers will use transverse and longitudinal sections. The presence of choline acetil transferase (ChAT) will also be investigated, using phrenic nerves as controls.Because it was demonstrated in HF following myocardial infarction (MI) an attenuation of the baroreflex, Project 2 will examine the hemodynamic responses - arterial pressure (AP) and heart rate (HR) - to electrical stimulation of the ADN in conscious HF rats, in order to identify which segment - afferences, central nervous system, efferences (sympathetic and parasympathetic) - of the baroreflex arch is deranged. Moreover, conscious HF rats will be submitted to pharmacological blockade with atropine, atenolol and prazosin to evaluate the role played by autonomic efferences (sympathetic and parasympathetic) in the regulation of AP and HR.Stem cell therapy has shown promising results after MI in both, patients and experimental animals, especially those using mesenchymal stem cells (MSC), which has shown potential pro-angiogenic, anti-fibrotic and immunomodulatory effect. However, studies have shown differentiation of MSC into adrenergic nerves in the heart, which might have deleterious outcome, especially in MI. Therefore, Project 3 aims to examine the effect of MSC on cardiac sympathovagal balance in HF rats following MI. The size of MI will be assessed by single photon emission computed tomography (SPECT), while the cardiac function will be assessed by isotopic cardiac ventriculography.The examination of HF after MI proposed in the current study involves also a new methodological approach, i.e. genetically modified mice: knockout for the gene of serino-protease elastase-2 (ELA2) and knockdown for the gene of vesicular acetylcholine transporter (VAChT KDHOM).Recent studies have demonstrated the presence of alternative pathways for angiotensin converting enzyme (ACE) to yield angiotensin II (Ang II) in tissues of several species including humans. One of these pathways is the ELA-2, which is widely distributed in several rodent organs. To evaluate the importance of ELA-2, it was developed a mouse with total deletion (knockout) of this enzyme. Therefore, the aim of Subproject 4A is to characterize the hemodynamic parameters (AP and HR), autonomic balance and cardiovascular and renal structures of mice with total deletion (knockout) of ELA-2 before and after the development of HF induced by MI.A knockdown homozygous mouse for the gene of vesicular acetylcholine transporter (VAChT KDHOM) has been developed. This model is particularly suitable for the investigation of parasympathetic function under pathological condition such as HF. Therefore, the Subproject 4B will evaluate in VAChT KDHOM mice, after MI, the effects of the attenuation of the cholinergic function on the hemodynamic parameters (AP and HR) and the sympathovagal balance upon cardiovascular regulation, by means of telemetry. In addition, it will be also examined the cardiovascular responses of these genetically modified mice during the development of HF. (AU)

Scientific publications

(28)

(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)

OMOTO, ANA CAROLINA M.; LATARO, RENATA M.; SILVA, THAIS M.; SALGADO, HELIO CESAR; FAZAN JR, RUBENS; VIRGILIO SILVA, LUIZ EDUARDO. Heart rate fragmentation, a novel approach in heart rate variability analysis, is altered in rats 4 and 12 weeks after myocardial infarction. MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING, v. 59, n. 11-12, OCT 2021. (13/20549-7)

BROGNARA, FERNANDA; FELIPPE, IGOR S. A.; SALGADO, HELIO C.; PATON, JULIAN F. R.. Autonomic innervation of the carotid body as a determinant of its sensitivity: implications for cardiovascular physiology and pathology. Cardiovascular Research, v. 117, n. 4, p. 1015-1032, APR 1 2021. (18/16953-0, 13/20549-7, 17/05163-6)

BASSI, G. S.; KANASHIRO, A.; RODRIGUES, G. J.; CUNHA, F. Q.; COIMBRA, N. C.; ULLOA, L.. Brain Stimulation Differentially Modulates Nociception and Inflammation in Aversive and Non-aversive Behavioral Conditions. Neuroscience, v. 383, p. 191-204, JUL 15 2018. (13/08216-2, 12/04237-2, 13/20549-7, 11/20343-4)

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)

DURAND, MARINA T.; BECARI, CHRISTIANE; TEZINI, GEISA C. S. V.; FAZAN, JR., RUBENS; OLIVEIRA, MAURO; GUATIMOSIM, SILVIA; PRADO, VANIA F.; PRADO, MARCO A. M.; SALGADO, HELIO C.. Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 4, p. H655-H662, AUG 15 2015. (13/20549-7, 14/01089-8, 13/06452-0)

BECARI, CHRISTIANE; DURAND, MARINA T.; GUIMARAES, ALESSANDER O.; LATARO, RENATA M.; PRADO, CIBELE M.; DE OLIVEIRA, MAURO; CANDIDO, SARAI C. O.; PAIS, PALOMA; RIBEIRO, MAURICIO S.; BADER, MICHAEL; et al. Elastase-2, a Tissue Alternative Pathway for Angiotensin II Generation, Plays a Role in Circulatory Sympathovagal Balance in Mice. FRONTIERS IN PHYSIOLOGY, v. 8, MAR 23 2017. (13/20549-7)

VIRGILIO SILVA, LUIZ EDUARDO; AGUIAR SILVA, CARLOS ALBERTO; SALGADO, HELIO CESAR; FAZAN, JR., RUBENS. The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 312, n. 3, p. H469-H477, MAR 2017. (13/20549-7)

RODRIGUES DA SILVA, GREICE ANNE; DE AGUIAR MENDES, VANIA ALICE; GENARI, ADRIANA BORGES; CASTANIA, JACI AYRTON; SALGADO, HELIO CESAR; SASSOLI FAZAN, VALERIA PAULA. Recurrent Laryngeal Nerve Alterations in Developing Spontaneously Hypertensive Rats. LARYNGOSCOPE, v. 126, n. 1, p. E40-E47, JAN 2016. (13/01111-0, 13/20549-7)

VIRGILIO SILVA, LUIZ EDUARDO; LATARO, RENATA MARIA; CASTANIA, JACI AIRTON; AGUIAR SILVA, CARLOS ALBERTO; SALGADO, HELIO CESAR; FAZAN, JR., RUBENS; PORTA, ALBERTO. Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales. Journal of Applied Physiology, v. 123, n. 2, p. 344-351, AUG 2017. (13/20549-7, 11/12460-0)

BASSI, GABRIEL SHIMIZU; ULLOA, LUIS; SANTOS, VICTOR RODRIGUES; DEL VECCHIO, FLAVIO; DELFINO-PEREIRA, POLIANNA; RODRIGUES, GERSON JHONATAN; CASTANIA, JACI AIRTON; CUNHA, FERNANDO DE QUEIROZ; SALGADO, HELIO CESAR; CUNHA, THIAGO MATTAR; et al. Cortical stimulation in conscious rats controls joint inflammation. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 84, n. A, p. 201-213, JUN 8 2018. (13/20549-7, 13/08216-2, 11/20343-4, 12/04237-2)

VIRGILIO SILVA, LUIZ EDUARDO; MARTINS DIAS, DANIEL PENTEADO; AGUIAR DA SILVA, CARLOS ALBERTO; SALGADO, HELIO CESAR; FAZAN, JR., RUBENS. Revisiting the Sequence Method for Baroreflex Analysis. FRONTIERS IN NEUROSCIENCE, v. 13, JAN 23 2019. (13/20549-7)

LETÍCIA OLIVEIRA NERI; MILENA MENEZES DE AMORIM; STELLA ANDRADE RODRIGUES CAMPOS; LUCIANA SAYURI SANADA; VALÉRIA PAULA SASSOLI FAZAN. Hind Limb Sensory Innervation in Rats: Comparison between Sural and Saphenous Nerve Morphometry. INTERNATIONAL JOURNAL OF MORPHOLOGY, v. 33, n. 2, p. 743-750, 2015-06-00. (13/20549-7, 13/01111-0)

BROGNARA, FERNANDA; CASTANIA, JACI AIRTON; RIBEIRO, ALINE BARBOSA; SANTOS-JUNIOR, NILTON NASCIMENTO; SALGADO, HELIO CESAR. The Bezold-Jarisch Reflex and The Inflammatory Response Modulation in Unanesthetized Endotoxemic Rats. FRONTIERS IN PHYSIOLOGY, v. 12, SEP 20 2021. (13/20549-7, 20/06043-7, 18/10455-9, 18/20939-3, 17/05163-6)

CASTANIA, JACI A.; KATAYAMA, PEDRO L.; BROGNARA, FERNANDA; MORAES, DAVI J. A.; SABINO, JOAO PAULO J.; SALGADO, HELIO C.. Selective denervation of the aortic and carotid baroreceptors in rats. Experimental Physiology, v. 104, n. 9, p. 1335-1342, SEP 2019. (17/05163-6, 13/10484-5, 13/20549-7, 15/18511-7)

BROGNARA, FERNANDA; CASTANIA, JACI AIRTON; MARTINS DIAS, DANIEL PENTEADO; KANASHIRO, ALEXANDRE; SALGADO, HELIO CESAR. Time Course of Hemodynamic Responses to Different Doses of Lipopolysaccharide in Unanesthetized Male Rats. FRONTIERS IN PHYSIOLOGY, v. 10, JUN 25 2019. (11/20343-4, 17/05163-6, 13/20549-7)

RIBEIRO, ADRIANA B.; DE ARAUJO, CAMILA B.; SILVA, V, LUIZ EDUARDO; FAZAN-JUNIOR, RUBENS; SALGADO, HELIO C.; RIBEIRO, ALINE B.; FORTES, V, CAROLINE; BUENO, FRANK L.; DE OLIVEIRA, VIVIANE C.; PARANHOS, HELENA DE F. O.; et al. Hygiene protocols for the treatment of denture-related stomatitis: local and systemic parameters analysis-a randomized, double-blind trial protocol. Trials, v. 20, n. 1, NOV 29 2019. (13/20549-7)

BERTONCINI SIMOES, ANA LEDA; RODRIGUES SILVA, GREICE ANNE; GIORGETTO, CAROLINA; DO CARMO-CAMPOS, ELISABETE DE CASSIA; DIAS, FERNANDO JOSE; SASSOLI FAZAN, VALERIA PAULA. Substance P in Dorsal Root Ganglion Neurons in Young and Adult Rats, after Nociceptive Stimulation during the Neonatal Period. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology, v. 301, n. 5, p. 849-861, MAY 2018. (13/20549-7, 14/07253-4)

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 SHIMIZU; MARTINS DIAS, DANIEL PENTEADO; FRANCHIN, MARCELO; TALBOT, JHIMMY; REIS, DANIEL GUSTAVO; MENEZES, GUSTAVO BATISTA; CASTANIA, JACI AIRTON; GARCIA-CAIRASCO, NORBERTO; MORAES RESSTEL, LEONARDO BARBOSA; SALGADO, HELIO CESAR; et al. Modulation of experimental arthritis by vagal sensory and central brain stimulation. BRAIN BEHAVIOR AND IMMUNITY, v. 64, p. 330-343, AUG 2017. (15/20463-0, 13/20549-7, 13/08216-2, 11/20343-4, 12/04237-2)

RIBEIRO, ALINE BARBOSA; SANTOS-JUNIOR, NILTON NASCIMENTO; LUIZ, JOAO PAULO MESQUITA; DE OLIVEIRA, MAURO; KANASHIRO, ALEXANDRE; TAIRA, THAISE MAYUMI; FUKADA, SANDRA YASUYO; ALVES-FILHO, JOSE CARLOS; FAZAN JUNIOR, RUBENS; SALGADO, HELIO CESAR. Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis. SCIENTIFIC REPORTS, v. 10, n. 1, APR 23 2020. (18/20939-3, 13/20549-7, 18/10455-9)

LATARO, RENATA M.; IMORI, PRISCILLA F. M.; SANTOS, EMERSON S.; SILVA, V, LUIZ EDUARDO; DUARTE, RUBENS T. D.; SILVA, CARLOS A. A.; FALCAO, JULIANA P.; PATON, JULIAN F. R.; SALGADO, HELLO C.. Heart failure developed after myocardial infarction does not affect gut microbiota composition in the rat. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, v. 317, n. 3, p. G342-G348, SEP 2019. (13/20549-7)

PRADO, FERNANDA P.; DOS SANTOS, DANIELE O.; BLEFARI, VALDECIR; SILVA, CARLOS A.; MACHADO, JULIANO; KETTELHUT, ISIS DO CARMO; RAMOS, SIMONE G.; BARUFFI, MARCELO DIAS; SALGADO, HELIO C.; PRADO, CIBELE M.. Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure. PLoS One, v. 12, n. 12, DEC 21 2017. (12/23649-0, 16/21710-4, 09/17787-8, 13/20549-7, 10/19216-5, 09/54010-1)

MIEKO OMOTO, ANA CAROLINA; GAVA, FABIO NELSON; AGUIAR SILVA, CARLOS ALBERTO; SILVA, HADDER BATISTA; PARENTE, JULIANA MONTENEGRO; COSTA, RAFAEL MENEZES; CASTRO, MICHELE MAZZARON; TOSTES, RITA DE CASSIA; SALGADO, HELIO CESAR; FAZAN JR, RUBENS. Lack of scarring is not always a sign of cardiac health: Functional and molecular characterization of the rat heart's following chronic reperfusion. PLoS One, v. 13, n. 12, DEC 20 2018. (13/20549-7)

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)

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)

DAS GRACAS CORSI-ZUELLI, FABIANA MARIA; BROGNARA, FERNANDA; DA SILVA QUIRINO, GUSTAVO FERNANDO; HIROKI, CARLOS HIROJI; FAIS, RAFAEL SOBRANO; DEL-BEN, CRISTINA MARTA; ULLOA, LUIS; SALGADO, HELIO CESAR; KANASHIRO, ALEXANDRE; LOUREIRO, CAMILA MARCELINO. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Acetylcholine the Alpha-7 nicotinic Acetylcholine Receptor. FRONTIERS IN IMMUNOLOGY, v. 8, MAY 31 2017. (12/05178-0, 16/12195-9, 13/20549-7, 11/20343-4, 16/07641-0, 16/11988-5, 15/10378-6)

SANADA, LUCIANA SAYURI; TAVARES, MARCELO RODRIGO; SATO, KARINA LAURENTI; FERREIRA, RENATA DA SILVA; MAIA NEUBERN, MILENA CARDOSO; CASTANIA, JACI AYRTON; SALGADO, HELIO CESAR; SASSOLI FAZAN, VALERIA PAULA. Association of chronic diabetes and hypertension in sural nerve morphometry: an experimental study. DIABETOLOGY & METABOLIC SYNDROME, v. 7, FEB 15 2015. (13/01111-0, 13/20549-7, 09/16748-9)

VIRGILIO SILVA, LUIZ EDUARDO; LATARO, RENATA MARIA; CASTANIA, JACI AIRTON; AGUIAR DA SILVA, CARLOS ALBERTO; VALENCIA, JOSE FERNANDO; MURTA, JR., LUIZ OTAVIO; SALGADO, HELIO CESAR; FAZAN, JR., RUBENS; PORTA, ALBERTO. Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 311, n. 1, p. R150-R156, JUL 1 2016. (13/20549-7, 11/12460-0)