Escola Paulista de Medicina
Postgraduate Program in Pharmacology

CARDIOVASCULAR AND RENAL PHYSIOLOGY AND PHARMACOLOGY:Projects

Projects of the CARDIOVASCULAR AND RENAL PHYSIOLOGY AND PHARMACOLOGY Research Line of the Postgraduate Program in Pharmacology:

AUTONOMIC CARDIOVASCULAR CONTROL IN NORMALITY AND IN VARIOUS EXPERIMENTAL MODELS AND CLINICAL SITUATIONS (ARTERIAL HYPERTENSION, SEPSIS, OBESITY, NEPHROLITHIASIS, RENAL INSUFFICIENCY

AUTONOMIC CARDIOVASCULAR CONTROL IN NORMALITY AND IN VARIOUS EXPERIMENTAL MODELS AND CLINICAL SITUATIONS (ARTERIAL HYPERTENSION, SEPSIS, OBESITY, NEPHROLITHIASIS, RENAL INSUFFICIENCY

In these projects, the participation of the sympathetic nervous system in the control of blood pressure and renal function under normal conditions and in different experimental pathophysiological models such as: arterial hypertension, chronic renal failure, sleep disorders and obesity is studied. Possible mechanisms of sympathetic activation have been investigated. The direct recording of sympathetic nervous activity, in one or more territories, associated with molecular biology techniques has been one of the focuses of this line of research. In addition to experimental models, clinical situations in which the risk of cardiovascular disease is associated with changes in the autonomic nervous system and related mechanisms are also being evaluated.

Professor: Cassia Toledo Bergamaschi

CONTROL OF CARDIOVASCULAR AND RENAL SYSTEMS IN PHYSIOLOGICAL AND PHYSIOPATHOLOGICAL SITUATIONS, MOLECULAR, CELLULAR AND INTEGRATIVE MECHANISMS

CONTROL OF CARDIOVASCULAR AND RENAL SYSTEMS IN PHYSIOLOGICAL AND PHYSIOPATHOLOGICAL SITUATIONS, MOLECULAR, CELLULAR AND INTEGRATIVE MECHANISMS

Cardiovascular and renal diseases are the main causes of mortality in Brazil and worldwide. Increased sympathetic vasomotor activity and autonomic dysfunction are common in cardiovascular and renal pathophysiological conditions and are directly related to the severity of the disease, however, the mechanisms underlying such changes are poorly understood. We have investigated how the central nervous system controls the cardiovascular and renal systems. As the brain communicates with the kidneys, vessels and heart in pathophysiological situations such as arterial hypertension, heart failure and diabetes is the main focus of this line of research.

Professor: Ruy Ribeiro de Campos Junior

MECHANISMS INDUCING PANCREATIC CHANGES

MECHANISMS INDUCING PANCREATIC CHANGES

LaFiPE- Laboratório da Fisiologia do Pâncreas Endócrino 

Diabetes mellitus type 2 (DM2) is the metabolic disease more prevalent throughout the world and is characterized by chronic hyperglycemia with disorder in the metabolism of carbohydrates, fats and proteins, resulting from defects in insulin secretion, action or both. The pathophysiology of DM2 has been primarily associated with the increase in inflammatory sub-clinic framework and development of peripheral resistance to insulin. Many evidences show that the fetal and neonatal, embryonic development is influenced by adverse factors that affect pregnant women and are associated with health conditions of individuals in adulthood. The presence of hyperglycemia during pregnancy appears to be responsible for defects in glucose metabolism and function of pancreatic β cells of the offspring. Evidences  suggest that a hostile intrauterine environment leads to changes in the expression and function of the genes in the offspring and this mechanism seems to involve the expression of microRNAs. The aim of our laboratory is to study the impact of maternal hyperglycemia on the expression of miRNAs in offspring pancreatic islets at different stages of development and that could potentially be considered biomarkers of DM2 development in adulthood.

Professor: Aparecida Emiko Hirata

PHYSIOPHARMACOLOGY OF CARDIOVASCULAR SYSTEM DISEASES: ROLE OF ION CHANNELS

PHYSIOPHARMACOLOGY OF CARDIOVASCULAR SYSTEM DISEASES: ROLE OF ION CHANNELS

Our main goal is to understand the role of ion channels for the genesis of inherited and acquired cardiovascular diseases, such as pulmonary arterial hypertension, Chagas disease, and Long QT Syndrome Type 3. After identifying the importance of a given ion channel, we seek to identify new therapeutic agents that make it possible to correct the ion channel function. Another main interest of our laboratory is to conduct cardiotoxicity assays to evaluate the impact of pesticides on human ion channels and other compounds of economic relevance. 

Professor: Danilo Roman Campos

EXPERIMENTAL PATHOPHYSIOLOGY: ROLE OF CENTRAL MECHANISMS OF THE CARDIOVASCULAR AND RESPIRATORY CONTROL CHANGES INDUCED BY EXPERIMENTAL HYPERTENSION AND OBESITY

EXPERIMENTAL PATHOPHYSIOLOGY: ROLE OF CENTRAL MECHANISMS OF THE CARDIOVASCULAR AND RESPIRATORY CONTROL CHANGES INDUCED BY EXPERIMENTAL HYPERTENSION AND OBESITY

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 trainingprevents 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.

Professor: Eduardo Colombari

NEURAL REGULATION OF THE CARDIOVASCULAR AND RENAL SYSTEMS

NEURAL REGULATION OF THE CARDIOVASCULAR AND RENAL SYSTEMS

Studies have shown the strong neurogenic component in the development of several cardiovascular diseases in humans and experimental models. Renal denervation in hypertensive patients resistant to pharmacological treatment is an effective strategy for controlling blood pressure, which has been attributed to the interruption of sympathetic and afferent renal fibers. In research topic, we study the molecular and physiological mechanisms involved in the regulation of the cardiovascular and renal systems and neural mechanisms that contribute to sympathetic nervous hyperactivation in arterial hypertension, chronic kidney disease and obesity. We have focused mainly on markers of fibrosis and renal function and oxidative stress in the kidney and central nervous system.

Professor responsável: Erika Emy Nishi

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