Role of NAD(P)H oxidase in vascular dysfunction and increased blood pressure induced by ethanol consumption: involvement of oxidative stress and the vascular redox signaling

• Grant number: 13/15824-9
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2014
• End date: April 30, 2016
• 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

Abstract

Chronic ethanol consumption induces significant changes in the cardiovascular system, appearing as an important risk factor in the development of cardiovascular diseases such as hypertension. Despite the well-established relationship between ethanol intake and hypertension, the precise mechanism underlying this process occurs is not fully understood. The cardiovascular dysfunction associated with ethanol involves the formation of reactive oxygen species (ROS) and the reduced bioavailability of nitric oxide (NO). These responses are responsible for the endothelial/vascular dysfunction associated with ethanol consumption. Moreover, ethanol consumption reduces tissue antioxidant capacity. The enzyme NAD(P)H oxidase is the main source of ROS (superoxide anion and hydrogen peroxide) in the vasculature. The pathophysiological importance of NAD(P)H oxidase has been proven in various cardiovascular disorders, including hypertension. For example, some studies show that inhibition of NAD(P)H oxidase with apocynin prevents or reverses blood pressure increase and vascular remodeling. Besides inducing endothelial dysfunction, the ROS produced by NAD(P)H oxidase act as signaling molecules ("redox signaling"). ROS activate intracellular pathways such as the MAPKs (Mitogen-Activated Protein Kinases) and MMPs (matrix metalloproteinases) pathways that play an important role in intracellular signaling and vascular pathophysiology. Ethanol activates both MAPK and MMPs pathways, but this response appears to occur indirectly. The hypothesis of this study is that chronic ethanol consumption induces the production of ROS in the cardiovascular system via NAD(P)H oxidase. This process would result in reduced bioavailability of NO, the activation of MAPKs and MMPs pathways, abnormal vascular function and increased blood pressure. Therefore, the aim of this study is to evaluate the role of NAD(P)H oxidase in vascular dysfunction and increased blood pressure induced by ethanol consumption. (AU)

Scientific publications

(5)

(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)

GONZAGA, NATALIA A.; MECAWI, ANDRE S.; ANTUNES-RODRIGUES, JOSE; DE MARTINIS, BRUNO S.; PADOVAN, CLAUDIA M.; TIRAPELLI, CARLOS R.. Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats. ALCOHOL, v. 49, n. 1, p. 47-56, FEB 2015. (13/15824-9, 13/00808-8)

SIMPLICIO, JANAINA A.; DO VALE, GABRIEL T.; GONZAGA, NATALIA A.; LEITE, LETICIA N.; HIPOLITO, ULISSES V.; PEREIRA, CAMILA A.; TOSTES, RITA C.; TIRAPELLI, CARLOS R.. Reactive oxygen species derived from NAD(P) H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries. JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, v. 73, n. 1, p. 5-16, FEB 2017. (13/03965-7, 13/15824-9)

MARCHI, KATIA COLOMBO; CERON, CARLA SPERONI; MUNIZ, JAQUELINE J.; DE MARTINIS, BRUNO S.; TANUS-SANTOS, JOSE E.; TIRAPELLI, CARLOS RENATO. NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature. ALCOHOL AND ALCOHOLISM, v. 51, n. 5, p. 522-534, SEP 2016. (12/01147-2, 13/15824-9)

LEITE, LETICIA N.; DO VALE, GABRIEL T.; SIMPLICIO, JANAINA A.; DE MARTINIS, BRUNO S.; CARNEIRO, FERNANDO S.; TIRAPELLI, CARLOS R.. Ethanol-induced erectile dysfunction and increased expression of pro-inflammatory proteins in the rat cavernosal smooth muscle are mediated by NADPH oxidase-derived reactive oxygen species. European Journal of Pharmacology, v. 804, p. 82-93, JUN 5 2017. (13/15824-9)

DO VALE, GABRIEL T.; DA SILVA, CARLA B. P.; SOUSA, ARTHUR H.; GONZAGA, NATALIA A.; PARENTE, JULIANA M.; ARAUJO, KATIUSCIA M.; CASTRO, MICHELE M.; TIRAPELLI, CARLOS R.. Nebivolol Prevents Up-Regulation of Nox2/NADPH Oxidase and Lipoperoxidation in the Early Stages of Ethanol-Induced Cardiac Toxicity. Cardiovascular Toxicology, v. 21, n. 3, p. 224-235, MAR 2021. (13/15824-9)