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Possible connections between hypertension and hypercholesterolemia in relation to arteriosclerosis: inactivation paths of nitric oxide and oxidation of lipoproteins

Grant number: 97/05090-3
Support Opportunities:Research Projects - Thematic Grants
Start date: March 01, 1998
End date: August 31, 2002
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Dulcineia Saes Parra Abdalla
Grantee:Dulcineia Saes Parra Abdalla
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Eder Carlos Rocha Quintão

Abstract

Hypertension and hypercholesterolemia are well known risk factors for atherosclerosis development. However, the biochemical mechanisms that establish the connections between both risk factors in relation to the atherosclerotic process is still not elucidated. In essential hypertension either a low generation or an enhanced inactivated by of nitric oxide may be occurring. Nitric oxide may be inactivated by reaction with superoxide radical yielding peroxynitrite. The in vivo generation of peroxynitrite may have diverse consequences including the oxidation of lipoproteins that are directly involved in atherogenesis and atherosclerosis development. In hyperlipidemic states the increased number of lipoprotein particles may induce an enhanced generation of superoxide radical and nitric oxide by vascular endothelium favoring tlie inactivation of nitric oxide and the generation of peroxynitrite. This could contribute either to a disturbed endothelium-dependent vasorelaxation or to atherosclerosis development. Therefore, our goal is to investigate the formation of compounds that can indicate possible inactivation pathways of nitric oxide, such as nitrotyrosine formed by reaction of peroxynitrite with tyrosil residues and other biomarkers of nitric oxide reaction with plasma components (S-nitrosothiols, LONO and LOONO), as well as the oxidation of plasma lipoproteins to elucidate the relationship among these pathways with atherosclerosis development in hypertension and hyperlipidemic states. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (4)
(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)
PATRICIA MORIEL; FRIDA L PLAVNIK; MARIA T ZANELLA; MARCELO C BERTOLAMI; DULCINEIA SP ABDALLA. Lipid peroxidation and antioxidants in hyperlipidemia and hypertension. Biological Research, v. 33, n. 2, p. 105-112, . (97/05090-3)
DAMASCENO‚ N.R.T.; SEVANIAN‚ A.; APOLINÁRIO‚ E.; OLIVEIRA‚ J.; FERNANDES‚ I.; ABDALLA‚ D.S.P.. Detection of electronegative low density lipoprotein (LDL-) in plasma and atherosclerotic lesions by monoclonal antibody-based immunoassays. CLINICAL BIOCHEMISTRY, v. 39, n. 1, p. 28-38, . (97/05090-3)
PEREIRA‚ E.C.; BERTOLAMI‚ M.C.; FALUDI‚ A.A.; SALEM‚ M.; BERSCH‚ D.; ABDALLA‚ D.S.P.. Effects of simvastatin and L-arginine on vasodilation‚ nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects. Free Radical Research, v. 37, n. 5, p. 529-536, . (97/05090-3)
P. MORIEL; A. SEVANIAN; S. AJZEN; M.T. ZANELLA; F.L. PLAVNIK; H. RUBBO; D.S.P. ABDALLA. Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension. Brazilian Journal of Medical and Biological Research, v. 35, n. 11, p. 1301-1309, . (97/05090-3)

Filed patent(s) as a result of this research project

ANTICORPO MONOCLONAL ANTI-LDL ELETRONEGATIVA (LDL-); PROCESSO DE OBTENÇÃO DO ANTICORPO; CONJUNTOS DIAGNÓSTICO PARA DETECÇÃO DE LDL NO PLASMA SANGÜINEO E EM LESÕES ATEROSCLERÓTICAS; COMPOSIÇÃO FARMACÊUTICA PARA COMBATE E/OU PREVENÇÃO À DOENÇAS CRÔNICO-DEGENERATIVAS E MÉTODO DE APLICAÇÃO DOS FÁRMACOS PREPARADOS À BASE DO ANTICORPO NO COMBATE E PREVENÇÃO DE DOENÇAS CRÔNICO-DEGENERATIVAS PI0203233-3 - Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Universidade de São Paulo (USP) . Dulcineia Saes Parra Abdalla ; Elaine Apolinario ; Nágila Raquel Teixeira Damasceno - June 2002, 13