Role of AT1 receptors on ethanol withdrawal-induced hypertension and vascular oxidative stress

• Grant number: 15/22046-8
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2016
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Renato Tirapelli
• Grantee: Carlos Renato Tirapelli
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: José Antunes Rodrigues

Abstract

Total or partial interruption of ethanol consumption by alcoholics can lead to the onset of symptoms of varied intensity. According to the International Classification of Diseases (ICD-10 - 10th Edition; WHO) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV - 4th Edition, American Psychiatric Association) these symptoms are classified as the Alcohol Withdrawal Syndrome (AWS). Signs and symptoms of the AWS may vary in intensity and severity and include sweating, tremors, anxiety, agitation, seizures, hallucinations, delirium tremens, disorientation and high blood pressure. However, the mechanisms underlying the increase in blood pressure induced by ethanol withdrawal remain elusive. Ethanol withdrawal also leads to the activation of the renin-angiotensin system (RAS). In the vasculature, angiotensin (ANG) II, via AT1 receptors activation, induces the generation of reactive oxygen species (ROS), such as superoxide anion (O2-). ANG II-induced ROS generation in the vasculatures is mainly mediated by the enzyme NAD(P)H oxidase. The reaction of O2- with nitric oxide (NO) can lead to the generation of peroxynitrite (ONOO-) and consequent reduced bioavailability of NO and vascular dysfunction. Additionally, NAD(P)H oxidase-derived ROS can act as signaling molecules and activate intracellular pathways such as the MAPKs (mitogen-activated protein kinases) that play an important role in intracellular signaling and vascular pathophysiology. The increase in vascular oxidative stress can also lead to changes in tissue enzymatic antioxidant capacity. The hypothesis of this study is that ethanol withdrawal induces an increase on ANG II, which will in turn increase ROS generation via vascular NAD(P)H oxidase activation. This process would lead to a decrease on NO bioavailability, activation of MAPKs, decreased vascular antioxidant capacity, vascular dysfunction and hypertension. Therefore, the aim of this study is to evaluate the role of AT1 receptors on the vascular oxidative stress and increase in blood pressure induced by ethanol withdrawal. (AU)

Scientific publications

(11)

(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)

ASSIS, VICTOR O.; GONZAGA, NATALIA A.; SILVA, CARLA B. P.; PEREIRA, LUCAS C.; PADOVAN, CLAUDIA M.; TIRAPELLI, CARLOS R.. Ethanol Withdrawal Alters the Oxidative State of the Heart Through AT(1)-Dependent Mechanisms. ALCOHOL AND ALCOHOLISM, v. 55, n. 1, p. 3-10, JAN 2020. (15/22046-8, 13/00808-8)

SILVA, CARLA B. P.; GOMEZ, JULIETH P. S.; DO VALE, GABRIEL T.; SIMPLICIO, JANAINA A.; GONZAGA, NATALIA A.; TIRAPELLI, CARLOS R.. Interleukin-10 limits the initial steps of the cardiorenal damage induced by ethanol consumption. Life Sciences, v. 242, FEB 1 2020. (15/22046-8)

CERON, CARLA S.; DO VALE, GABRIEL T.; SIMPLICIO, JANAINA A.; RICCI, STHEFANY T.; DE MARTINIS, BRUNO S.; DE FREITAS, ANDRESSA; TIRAPELLI, CARLOS R.. Chronic ethanol consumption increases vascular oxidative stress and the mortality induced by sub-lethal sepsis: Potential role of iNOS. European Journal of Pharmacology, v. 825, p. 39-47, APR 15 2018. (15/22046-8)

PEREIRA, BRUNA PINHEIRO; DO VALLE, GABRIEL TAVARES; CORREA SALLES, BRUNO CESAR; MANCINI COSTA, KARLA CRISTINNE; ANGELO, MARILENE LOPES; LOBO TORRES, LARISSA HELENA; NOVAES, ROMULO DIAS; RUGINSK, SILVIA GRACIELA; TIRAPELLI, CARLOS RENATO; DE ARAUJO PAULA, FERNANDA BORGES; et al. Pyrrolidine dithiocarbamate reduces alloxan-induced kidney damage by decreasing nox4, inducible nitric oxide synthase, and metalloproteinase-2. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 393, n. 10, MAY 2020. (15/22046-8)

GONZAGA, NATALIA A.; DO VALE, GABRIEL T.; PARENTE, JULIANA M.; YOKOTA, RODRIGO; DE MARTINIS, BRUNO S.; CASARINI, DULCE E.; CASTRO, MICHELE M.; TIRAPELLI, CARLOS R.. Ethanol withdrawal increases blood pressure and vascular oxidative stress: a role for angiotensin type 1 receptors. JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION, v. 12, n. 7, p. 561-573, JUL 2018. (15/22046-8)

DO VALE, GABRIEL T.; LEONI, DRIELI; SOUSA, ARTHUR H.; GONZAGA, NATALIA A.; ULIANA, DANIELA L.; LA GATA, DAVI C.; RESSTEL, LEONARDO B.; PADOVAN, CLAUDIA M.; TIRAPELLI, CARLOS R.. Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT(1) receptors. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 23, n. 3, p. 10-pg., 2019-10-14. (15/22046-8)

DO VALE, GABRIEL T.; LEONI, DRIELI; SOUSA, ARTHUR H.; GONZAGA, NATALIA A.; ULIANA, DANIELA L.; LA GATA, DAVI C.; RESSTEL, LEONARDO B.; PADOVAN, CLAUDIA M.; TIRAPELLI, CARLOS R.. Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT(1) receptors. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, OCT 2019. (15/22046-8)

DO VALE, GABRIEL T.; GONZAGA, NATALIA A.; SIMPLICIO, JANAINA A.; TIRAPELLI, CARLOS R.. Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression. European Journal of Pharmacology, v. 799, p. 33-40, MAR 15 2017. (15/22046-8)

DO VALLE, GABRIEL TAVARES; RICCI, STHEFANY TEODORO; SILVA, ALESSANDRA OLIVEIRA; TIRAPELLI, CARLOS RENATO; CERON, CARLA SPERONI. Ethanol consumption increases renal dysfunction and mortality in a mice model of sub-lethal sepsis. Canadian Journal of Physiology and Pharmacology, v. 99, n. 7, p. 699-707, JUL 2021. (15/22046-8)

DO VALE, GABRIEL T.; SIMPLICIO, JANAINA A.; GONZAGA, NATALIA A.; YOKOTA, RODRIGO; RIBEIRO, AMANDA A.; CASARINI, DULCE E.; DE MARTINIS, BRUNO S.; TIRAPELLI, CARLOS R.. Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol. ATHEROSCLEROSIS, v. 274, p. 67-76, JUL 2018. (15/22046-8)

GONZAGA, NATALIA A.; AWATA, WANESSA M. C.; TANUS-SANTOS, JOSE E.; PADOVAN, JULIO C.; TIRAPELLI, CARLOS R.. Mechanisms underlying vascular hypocontractility induced by ethanol withdrawal: Role of cyclooxygenase 2-derived prostacyclin. European Journal of Pharmacology, v. 847, p. 103-112, MAR 15 2019. (15/22046-8, 13/00808-8)