Decreased expression of neuronal nitric oxide synthase contributes to the endothelial dysfunction associated with cigarette smoking in human

Autor(es)

Costa, Eduardo D. ^[1] ; Silva, Josiane F. ^{[1, 2]} ; Garcia, Daniela C. ^[1] ; Wainstein, Alberto J. ^[3] ; Rezende, Bruno A. ^[3] ; Tostes, Rita C. ^[2] ; Teixeira, Mauro M. ^[4] ; Cortes, Steyner F. ^[5] ; Lemos, Virginia S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, Sao Paulo - Brazil

^[3] Med Sci Coll, Postgrad Inst, Dept Hlth Sci, Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil

^[5] Univ Fed Minas Gerais, Inst Biol Sci, Dept Pharmacol, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 98, p. 20-28, MAY 1 2020.
• Citações Web of Science: 0

Resumo

Endothelial nitric oxide synthase (eNOS) malfunctioning has been proposed to contribute to the endothelial damage produced by cigarette. Besides eNOS, neuronal NOS (nNOS) is also expressed in most vascular tissues and plays an important role in the endothelium-dependent vascular relaxation. We hypothesize that nNOS may contribute to the endothelium dysfunction produced by cigarette in smokers. Vascular function was assessed in human resistance mesenteric arteries using a wire myograph, the level of protein expression by Western blot, eNOS and nNOS localization by immunofluorescence. Measurement of NO was assessed by fluorescence microscopy. Arteries of smokers showed impaired endothelium-dependent vascular relaxation in response to acetylcholine. Pharmacological nonselective blockade of NOS with L-NAME and selective nNOS blockade with inhibitor 1 reduced the relaxation of the mesenteric artery of both smokers and nonsmokers. Interestingly, the inhibitory effect of NOS inhibitors was greater in nonsmokers than in smokers. The expression of total nNOS and eNOS and the level of phosphorylation at eNOS-pSer(1177) were reduced in arteries of smokers as compared with nonsmokers. No differences between groups were observed in the expression of total COX-1, COX-2, catalase and SOD-1. Immunofluorescence analysis showed the presence of nNOS in the vascular endothelium in both groups. Acetylcholine-induced NO production was impaired in arteries from smokers as compared to nonsmokers. Selective inhibition of nNOS caused a decreased in NO production, which was greater in nonsmokers than in smokers. Our data show that a decrease in nNOS expression contributes to the endothelial dysfunction caused by cigarette smoking in human. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/16207-1 - Centro de Pesquisa em Doenças Inflamatórias - CRID
• Beneficiário: Josiane Fernandes da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado