Nitric oxide donors, nitrite and nonsteroidal antiinflammatory agents combined with nitric oxide

• Grant number: 09/17607-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2010
• End date: July 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Lusiane Maria Bendhack
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Nitric oxide (NO) donors such as organic nitrates are used as pharmacological tool to investigate the physiological effect of NO and its effect in the cardiovascular diseases treatment. The nitrates have sudden effect, they are safe drugs and the side effects are not well known. However, in the last years, it has been reported that the treatment with nitroglycerin (NTG) induces endothelium damage. In vivo and in vitro studies have demonstrated its therapeutic limitation due to tolerance that is defined as the hemodynamic and antiischemic failed effect after chronic treatment. The causes of tolerance are not clearly understood. However, it seems to be due to multiple factors, including enzymatic biotransformation of NTG to NO, increased levels of reactive oxygen species (ROS), decreased activity of the enzyme soluble guanylyl-cyclase (sGC) and/or overexpression of phosphodiesterases (PDEs). Tolerance has been related only to organic nitrates, but it is not known if it also occurs for other NO donors. Recently, it was reported that nitrite is considered a NO donor that can activate sGC and produce vasodilatation, as well the nonsteroidal anti-inflammatory associated to NO (NO-NSAIDS). Considering that nitrates are NO donors that induce tolerance, the present study aims to investigate if the compounds NO donors, nitrite and NO-NSAIDS can induce tolerance and cross-tolerance in vitro in denuded or intact endothelium- isolated aorta. Then, the cellular mechanisms involved in the tolerance will be studied. (AU)

Scientific publications

(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)

DINIZ, MARIANA C.; OLIVON, VANIA C.; TAVARES, LIVIA D.; SIMPLICIO, JANAINA A.; GONZAGA, NATALIA A.; DE SOUZA, DANIELE G.; BENDHACK, LUSIANE M.; TIRAPELLI, CARLOS R.; BONAVENTURA, DANIELLA. Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids. Life Sciences, v. 176, p. 26-34, MAY 1 2017. (09/17607-0)